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Tetraodon nigroviridis as a nonlethal model of infectious spleen and kidney necrosis virus (ISKNV) infection
Xu Xiaopeng; Huang Lichao; Weng Shaoping; Wang Jing; Lin Ting; Tang Junliang; Li Zhongsheng; Lu Qingxia; Xia Qiong; Yu Xiaoqiang; He Jianguo
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. We have previously established a high mortality ISKNV infection model of zebrafish (Danio rerio). In this study, a nonlethal Tetraodon nigroviridis model of ISKNV infection was established. ISKNV infection did not cause lethal disease in Tetraodon but could infect almost all the organs of this species. Electron microscopy showed ISKNV particles were present in infected tissues. Immunofluorescence and quantitative real-time PCR analysis showed that nearly all the virions and infected cells were cleared at 14 d postinfection. The expression profiles of interferon-{gamma} and tumor necrosis factor-{alpha} gene in response to ISKNV infection were significantly different in Tetraodon and zebrafish. The establishment of the nonlethal Tetraodon model of ISKNV infection can offer a valuable tool complementary to the zebrafish infection model for studying megalocytivirus disease, fish immune systems, and viral tropism.
A zebrafish (Danio rerio) model of infectious spleen and kidney necrosis virus (ISKNV) infection
Xu Xiaopeng; Zhang Lichun; Weng Shaoping; Huang Zhijian; Lu Jing; Lan Dongming; Zhong Xuejun; Yu Xiaoqiang; Xu Anlong He Jianguo
Zebrafish is a model animal for studies of genetics, development, toxicology, oncology, and immunology. In this study, infectious spleen and kidney necrosis virus (ISKNV) was used to establish an infection in zebrafish, and the experimental conditions were established and characterized. Mortality of adult zebrafish infected with ISKNV by intraperitoneal (i.p.) injection exceeded 60%. ISKNV can be passed stably in zebrafish for over ten passages. The ailing zebrafish displayed petechial hemorrhaging and scale protrusion. Histological analysis of moribund fish revealed necrosis of tissue and enlarged cells in kidney and spleen. The real-time RT-PCR analysis of mRNA level confirmed that ISKNV was replicated in zebrafish. Immunohistochemistry and immunofluorescence analyses further confirmed the presence of ISKNV-infected cells in almost all organs of the infected fish. Electron microscope analyses showed that the ISKNV particle was present in the infected tissues. The establishment of zebrafish infection model of ISKNV can offer a valuable tool for studying the interactions between ISKNV and its host.
Molecular confirmation of infectious spleen and kidney necrosis virus (ISKNV) in farmed and imported ornamental fish in Australia.
Mohr, Peter G; Moody, Nicholas J G; Williams, Lynette M; Hoad, John; Cummins, David M; Davies, Kelly R; StJ Crane, Mark
Viruses of the genus Megalocytivirus have not been detected in wild populations of fish in Australia but circulate in imported ornamental fish. In 2012, detection of a megalocytivirus in healthy platys Xiphophorus maculatus was reported from a farm in Australia during surveillance testing as part of a research project undertaken at the University of Sydney. Confirmatory testing of the original samples at the AAHL Fish Diseases Laboratory verified the presence of an infectious spleen and kidney necrosis virus (ISKNV)-like virus. Additional sampling at the positive farm confirmed the persistence of the virus in the platys, with 39 of 265 (14.7%) samples testing positive. Comparison of 3 separate gene regions of the virus with those of ISKNV confirmed the detection of a virus indistinguishable from ISKNV. Subsequently, ISKNV was also detected in a range of imported ornamental fish from several countries between 2013 and 2014, by screening with real-time PCR and confirmation by conventional PCR and sequence analysis. Accordingly, the current importation of live ornamental fish acts as a potential perpetual source for the establishment of ISKNV viruses within Australia. The testing of the farmed and imported ornamental fish verified the utility of the probe-based real-time PCR assay for screening of ornamental fish for Megalocytivirus. PMID:26480913
First outbreak of an infection with infectious spleen and kidney necrosis virus (ISKNV) in ornamental fish in Germany.
Jung-Schroers, Verena; Adamek, Mikolaj; Wohlsein, Peter; Wolter, Jan; Wedekind, Helmut; Steinhagen, Dieter
In 2014, infectious spleen and kidney necrosis virus (ISKNV), a member of the genus Megalocytivirus, was detected for the first time in ornamental fish in Germany. Since 2013, angelfish Pterophyllum spp. originating from Colombia have experienced significant epizootics in a number of German retailers' facilities. The diseased fish showed symptoms such as increased ventilation, swollen gills, and ulcerations of the skin. In 2014, diseased angelfish P. altum and platys Xiphophorus maculatus maintained in the same recirculating system were examined. Histopathological lesions included hypertrophic cells, single-cell necrosis, and an inflammatory infiltration of granulocytes, lymphocytes, and macrophages in liver, spleen, and kidney. Transmission electron microscopy revealed the presence of numerous polygonal viral particles (150 nm in diameter) within the cytoplasm of enlarged cells. A PCR assay for the detection of megalocytiviruses amplified 777 bp of major capsid protein gene that was 100% identical to ISKNV. This is the first report of an ISKNV outbreak in Germany that most probably was introduced by infected angelfish from Colombia. To our knowledge, this is the first report of ISKNV detected in fish imported from South America. Given the lethal nature of megalocytiviruses, proper biosecurity would seem prudent in countries like Germany where these emerging pathogens are not established. PMID:27225207
A microRNA from infectious spleen and kidney necrosis virus modulates expression of the virus-mock basement membrane component VP08R.
Yan, Muting; He, Jianhui; Zhu, Weibin; Zhang, Jing; Xia, Qiong; Weng, Shaoping; He, Jianguo; Xu, Xiaopeng
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. Infection of ISKNV is characterized by a unique pathological phenomenon in that the infected cells are attached by lymphatic endothelial cells (LECs). ISKNV mediates the formation of a virus-mock basement membrane (VMBM) structure on the surface of infected cells to provide attaching sites for LECs. The viral protein VP08R is an important component of VMBM. In this study, a novel ISKNV-encoded microRNA, temporarily named ISKNV-miR-1, was identified. ISKNV-miR-1 is complementary to the VP08R-coding sequence and can modulate VP08R expression through reducing its mRNA level. This suggests that formation of VMBM may be under fine regulation by ISKNV. PMID:26896933
Infectious spleen and kidney necrosis virus (a fish iridovirus) enters Mandarin fish fry cells via caveola-dependent endocytosis.
Guo, Chang-Jun; Wu, Yan-Yan; Yang, Li-Shi; Yang, Xiao-Bo; He, Jian; Mi, Shu; Jia, Kun-Tong; Weng, Shao-Ping; Yu, Xiao-Qiang; He, Jian-Guo
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus from the family Iridoviridae. Megalocytiviruses have been implicated in more than 50 fish species infections and currently threaten the aquaculture industry, causing great economic losses in China, Japan, and Southeast Asia. However, the cellular entry mechanisms of megalocytiviruses remain largely uncharacterized. In this study, the main internalization mechanism of ISKNV was investigated by using mandarin fish fry (MFF-1) cells. The progression of ISKNV infection is slow, and infection is not inhibited when the cells are treated with ammonium chloride (NH(4)Cl), chloroquine, sucrose, and chlorpromazine, which are inhibitors of clathrin-dependent endocytosis. The depletion of cellular cholesterol by methyl-β-cyclodextrin results in the significant inhibition of ISKNV infection; however, the infection is resumed with cholesterol replenishment. Inhibitors of caveolin-1-involved signaling events, including phorbol 12-myristate 13-acetate (PMA), genistein, and wortmannin, impair ISKNV entry into MFF-1 cells. Moreover, ISKNV entry is dependent on dynamin and the microtubule cytoskeleton. Cofraction analysis of ISKNV and caveolin-1 showed that ISKNV colocates with caveolin-1 during virus infection. These results indicate that ISKNV entry into MFF-1 cells proceeds via classical caveola-mediated endocytosis and is dependent on the microtubules that serve as tracks along which motile cavicles may move via a caveola-caveosome-endoplasmic reticulum (ER) pathway. As a fish iridovirus, ISKNV entry into MFF-1 cells is different from the clathrin-mediated endocytosis of frog virus 3 entry into mammalian cells (BHK-21) at 28°C, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection. PMID:22171272
Immunological evaluation of Vibrio alginolyticus, Vibrio harveyi, Vibrio vulnificus and infectious spleen and kidney necrosis virus (ISKNV) combined-vaccine efficacy in Epinephelus coioides.
Huang, Zhijian; Tang, Jingjing; Li, Mei; Fu, Yacheng; Dong, Chuanfu; Zhong, Jiang F; He, Jianguo
Combined vaccines are immunological products intended for immunization against multifactorial infectious diseases caused by different types or variants of pathogens. In this study, the effectiveness of Vibrio alginolyticus (Va), Vibrio harveyi (Vh), Vibrio vulnificus (Vv) and infectious spleen and kidney necrosis virus (ISKNV), an iridovirus, combined-vaccine (Vibrio and ISKNV combined vaccines, VICV), Va+Vh+Vv inactive vaccine (VIV) and ISKNV whole cell inactive vaccine (IWCIV) in Epinephelus coioides were evaluated using various immunological parameters including antibody titer, serum lysozyme activity (LA), respiratory burst (RB) activity, bactericidal activity (BA) and relative percentage survival (RPS). E. coioides immunized with VICV and challenged with Va+Vh+Vv+ISKNV had an RPS of 80%. The RPS was 73.3% in E. coioides immunized with VIV and challenged with Va+Vh+Vv. E. coioides immunized with IWCIV and challenged with ISKNV had an RPS of 69.6%. Serum LA in the vaccinated group was significantly higher than the control group on days 21 and 28 post-vaccination (P<0.01). The RB activity of head kidney cells in the vaccinated group was significantly higher (P<0.01) compared to that in the control group. However, RB activity of spleen cells in the vaccinated group and the control group were not significantly different (P>0.05). After immunization with VICV, BA values of blood leucocytes and head kidney cells increased significantly more than spleen cells. BA value of blood leucocytes was higher than that in head kidney cells. There were distinct difference between BA values in head kidney cells and in spleen cells (P<0.05) as well as between BA value of blood leucocytes and head kidney cells (P<0.01). E. coioides vaccinated with VICV have significantly higher antibody levels than control groupers (P<0.01). Our study suggests that the VICV candidate can effectively protect groupers against multiple bacterial and viral pathogens. PMID:23010220
Protein encoded by ORF093 is an effective vaccine candidate for infectious spleen and kidney necrosis virus in Chinese perch Siniperca chuatsi.
Li, Ningqiu; Fu, Xiaozhe; Guo, Huizhi; Lin, Qiang; Liu, Lihui; Zhang, Defeng; Fang, Xiang; Wu, Shuqin
Infectious spleen and kidney necrosis virus (ISKNV) is the causative agent of a disease causing high mortality and economic losses in Chinese perch, Siniperca chuatsi in China. Little information about the antigenicity of ISKNV proteins is available. In this study the ORF093 gene of ISKNV was cloned into the prokaryotic expression vector pET32a(+) and eukaryotic expression vector pcDNA3.1(+), and designated as pET-093 and pcDNA-093, respectively. A recombinant 51-kDa protein was detected in Escherichia coli BL21 (harboring pET-093) after IPTG inducement. Polyclonal antibodies were raised in rabbits against the purified ORF093 protein and the reaction of the antibodies was confirmed by western blotting using the purified recombinant protein. Expression of the pcDNA-093 in muscle tissue of vaccinated fish was confirmed by western blotting. The protection efficacy of ORF093 was investigated and results showed that cumulative mortality of Chinese perch was significant differences between immune groups and control (P<0.05) after ISKNV challenge, and the RPS value of 093 recombinant protein, pcDNA093 and pcDNA093+MCP was 47%, 50% and 57%. The results suggested that ORF093 is an effective vaccine candidate for ISKNV and it can be used in the control of ISKNV disease in Chinese perch. PMID:25462463
Early protein ORF086 is an effective vaccine candidate for infectious spleen and kidney necrosis virus in mandarin fish Siniperca chuatsi.
Fu, Xiaozhe; Li, Ningqiu; Lin, Qiang; Guo, Huizhi; Liu, Lihui; Huang, Zhibin; Wu, Shuqin
Infectious spleen and kidney necrosis virus (ISKNV) has caused significant loss in the Mandarin fish (Siniperca chuatsi) aquaculture industry. Vaccination is an important measure to prevent fatal ISKNV infection. In this study, the ORF086 gene encoding an early protein helicase of ISKNV was cloned into the prokaryotic pET32a (+) and eukaryotic pcDNA3.1 (+) expression vectors and designated as pET086 and pcDNA086, respectively. A recombinant 36 kDa protein was detected in Escherichia coli BL21 (harboring pET086) after isopropyl β-d-1-thiogalactopyranoside (IPTG) induction. Polyclonal antibodies against the purified ORF086 protein were raised in rabbits. The antibody reaction and the pcDNA086 expression in muscle tissues of vaccinated fish were confirmed using Western blot analysis. The protective efficacy of ORF086 was also investigated. The cumulative mortality rates of Mandarin fish were significantly different between immune and control groups (P < 0.05) after ISKNV challenge. The relative percentage survival (RPS) values of the recombinant ORF086 protein emulsified with ISA763A adjuvant and pcDNA086 added with QCDC adjuvant were 73% and 63%, respectively. Transcriptional analysis of non-specific and specific immune related genes revealed that the expression levels of IRF-7, IRAK1, Mx, Viperin, and IgM were strongly up-regulated in the vaccinated groups post-immunization. In particular, the expression levels in the QCDC + pcDNA086 group was higher than those in the control groups (P < 0.05). These results indicated that the early protein ORF086 could be an effective antigen candidate for controlling ISKNV disease in Mandarin fish. PMID:26099219
Morphology of certain viruses of Salmonid fishes. II. In vivo studies of infectious Hematopoietic Necrosis Virus
Amend, Donald F.; Chambers, Velma C.
Juvenile sockeye salmon (Oncorhynchus nerka) were injected with the infectious hematopoietic necrosis (IHN) virus, and tissue samples from the anterior kidney, spleen, liver, intestine, and pyloric caeca of moribund fish were prepared for electron microscopy. Bullet-shaped virus particles measuring 158 × 90 mμ were observed in the hematopoietic tissues of the anterior kidney and spleen. Virus particles were also observed in the outer connective tissues of the pancreas or pyloric caeca, or both. No virus was found in the intestine or liver. The healthy appearance of erythrocytes, reticular cells, and endothelial cells in necrotic areas of the spleen and anterior kidney, and the absence of lymphocytes in these areas, suggested that lymphocytes might be one source of the virus.
Experimental Papillary Necrosis of the Kidney
Wyllie, R. G.; Hill, G. S.; Murray, G.; Ramsden, P. W.; Heptinstall, R. H.
Reserpine is able to exert a pronounced inhibitory effect on the development of papillary necrosis following the administration of bromoethylamine hydrobromide to the rat. This inhibitory effect has been observed using light microscopy, histochemistry, indigo carmine excretion and urine output. These observations suggest that vasoconstriction may play a significant role in the pathogenesis of papillary necrosis, but the evidence for this is incomplete. ImagesFig 1Fig 2Fig 3Fig 4Fig 5Fig 6 PMID:4114974
Thermal inactivation of infectious hematopoietic necrosis and infectious pancreatic necrosis virus
Gosting, L.; Gould, R.W.
A plaque assay was used to follow the inactivation kinetics of infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus in cell culture media at various temperatures. Inactivation of infectious hematopoietic necrosis virus in a visceral organ slurry was compared with that in culture media.
Detection of dwarf gourami iridovirus (Infectious spleen and kidney necrosis virus) in populations of ornamental fish prior to and after importation into Australia, with the first evidence of infection in domestically farmed Platy (Xiphophorus maculatus).
Rimmer, Anneke E; Becker, Joy A; Tweedie, Alison; Lintermans, Mark; Landos, Matthew; Stephens, Fran; Whittington, Richard J
The movement of ornamental fish through international trade is a major factor for the transboundary spread of pathogens. In Australia, ornamental fish which may carry dwarf gourami iridovirus (DGIV), a strain of Infectious spleen and kidney necrosis virus (ISKNV), have been identified as a biosecurity risk despite relatively stringent import quarantine measures being applied. In order to gain knowledge of the potential for DGIV to enter Australia, imported ornamental fish were sampled prior to entering quarantine, during quarantine, and post quarantine from wholesalers and aquatic retail outlets in Australia. Samples were tested by quantitative polymerase chain reaction (qPCR) for the presence of megalocytivirus. Farmed and wild ornamental fish were also tested. Megalocytivirus was detected in ten of fourteen species or varieties of ornamental fish. Out of the 2086 imported gourami tested prior to entering quarantine, megalocytivirus was detected in 18.7% of fish and out of the 51 moribund/dead ornamental fish tested during the quarantine period, 68.6% were positive for megalocytivirus. Of fish from Australian wholesalers and aquatic retail outlets 14.5% and 21.9%, respectively, were positive. Out of 365 farmed ornamental fish, ISKNV-like megalocytivirus was detected in 1.1%; these were Platy (Xiphophorus maculatus). Megalocytivirus was not detected in free-living breeding populations of Blue gourami (Trichopodus trichopterus) caught in Queensland. This study showed that imported ornamental fish are vectors for DGIV and it was used to support an import risk analysis completed by the Australian Department of Agriculture. Subsequently, the national biosecurity policy was revised and from 1 March 2016, a health certification is required for susceptible families of fish to be free of this virus prior to importation. PMID:26452601
Progressive outer retinal necrosis in immunocompromised kidney allograft recipient.
Turno-Kręcicka, A; Boratyńska, M; Tomczyk-Socha, M; Mazanowska, O
Ocular complications in patients who underwent renal transplantation are attributed to side effects of the immunosuppressive regimen. Progressive outer retinal necrosis (PORN) syndrome is a clinical variant of necrotizing herpetic retinopathy and it occurs almost exclusively in patients with acquired immunodeficiency syndrome. We present a case of a human immunodeficiency virus-negative patient who underwent renal transplant and, after a few years, developed bilateral PORN associated with viral infections. Varicella zoster virus (VZV) and BK virus were identified by polymerase chain reaction from the vitreous fluid. It is unclear which of the viruses identified had the dominant role in the pathogenesis of PORN and other organ damage, or whether their actions were synergistic. Adequate antiviral immune surveillance, as well as pre-transplant vaccination against VZV, may reduce the incidence of VZV infection and its complications. PMID:25846017
Necrosis of the femoral head after kidney transplantation.
Lausten, G S; Lemser, T; Jensen, P K; Egfjord, M
We reviewed the medical records of 750 patients (445 men, 305 women), who had received a kidney transplant during the period 1968-1995, for any sign of necrosis of the femoral head. For post-operative immunosuppression, 374 patients had received high-dose corticosteroids (average 12.5 g during the first year post-operatively), while 376 patients had received low-dose corticosteroids (average 6.5 g during the first year post-operatively) and cyclosporin A. Survival curves according to Kaplan and Meier (J Am Stat Ass 1958: 53: 457-481) were constructed. In the high-dose steroid group, 42/374 patients (11.2%) developed femoral head necrosis, at an average of 26.2 months post-transplantation. In the low-dose steroid group, only 19/376 (5.1%) patients developed this complication, at an average of 20.5 months post-transplantation. This difference in numbers of femoral head necroses was highly significant (p < 0.005). We conclude that steroid doses should be minimized whenever feasible in post-transplant immunosuppression therapy. PMID:9850453
Detection and transmission of infectious hematopoietic necrosis virus in rainbow trout
Amend, Donald F.
Detection and transmission of Infectious Hematopoietic Necrosis Virus in rainbow trout (Salmo gairdneri) was studied at a commercial trout hatchery. Transmission of virus was demonstrated via water, feed and contaminated eggs. If eggs from carrier females were incubated several weeks in virus-free water, the resulting fry did not become infected. However, if fry subsequently became infected they were lifetime carriers. Infectious virus was readily detectable in most tissues of moribund fish; in carriers it was detected in sex products of spawning fish, and in samples from the intestine of post-spawning fish, but not in samples from blood, feces, kidney, or liver. The carrier rate was not significantly different between sexes. It was concluded that adult carriers are the reservoir of infection and that transmission occurs primarily when carriers shed virus and expose susceptible fish or eggs.
Carrot yellow leaf virus Is Associated with Carrot Internal Necrosis
Adams, Ian P.; Skelton, Anna; Macarthur, Roy; Hodges, Tobias; Hinds, Howard; Flint, Laura; Nath, Palash Deb; Boonham, Neil; Fox, Adrian
Internal necrosis of carrot has been observed in UK carrots for at least 10 years, and has been anecdotally linked to virus infection. In the 2009 growing season some growers had up to 10% of yield with these symptoms. Traditional diagnostic methods are targeted towards specific pathogens. By using a metagenomic approach with high throughput sequencing technology, other, as yet unidentified causes of root necrosis were investigated. Additionally a statistical analysis has shown which viruses are most closely associated with disease symptoms. Carrot samples were collected from a crop exhibiting root necrosis (102 Affected: 99 Unaffected) and tested for the presence of the established carrot viruses: Carrot red leaf virus (CtRLV), Carrot mottle virus (CMoV), Carrot red leaf associated viral RNA (CtRLVaRNA) and Parsnip yellow fleck virus (PYFV). The presence of these viruses was not associated with symptomatic carrot roots either as single viruses or in combinations. A sub-sample of carrots of mixed symptom status was subjected to MiSeq sequencing. The results from these tests suggested Carrot yellow leaf virus (CYLV) was associated with symptomatic roots. Additionally a novel Torradovirus, a novel Closterovirus and two novel Betaflexiviradae related plant viruses were detected. A specific diagnostic test was designed for CYLV. Of the 102 affected carrots, 98% were positive for CYLV compared to 22% of the unaffected carrots. From these data we conclude that although we have yet to practically demonstrate a causal link, CYLV appears to be strongly associated with the presence of necrosis of carrots. PMID:25365290
Testing of male sockeye salmon (Oncorhynchus nerka) and steelhead trout (Salmo gairdneri) for infectious hematopoietic necrosis virus
Mulcahy, D.; Pascho, R.J.; Batts, W.N.
Infectious hematopoietic necrosis (IHN) virus has been isolated only rarely from whole milt samples of male sockeye salmon (Oncorhynchus nerka). In 3 yr of testing, virus incidences in males ranged from 0 to 13% when milt was sampled but were 60–100% with spleen or kidney. When IHN virus was isolated from sockeye salmon milt at titers less than 3.00 log10 plaque-forming units (pfu)/mL, the level of virus in the kidney or spleen exceeded 7.00 log10 pfu/g. Higher rates of IHN virus isolation from kidney or spleen than from milt were also generally found in steelhead trout (Salmo gairdneri), although the differences were less pronounced than in sockeye salmon. Furthermore, virus was sometimes isolated from steelhead trout milt when the level of virus in kidney or spleen samples was very low, and was recovered from some milt samples when none was isolated from the corresponding spleen sample. When male salmonids are tested for IHN virus, kidney or spleen samples are superior to whole milt, but milt should be included for critical examinations.
Bean Common Mosaic Virus and Bean Common Mosaic Necrosis Virus (Genus Potyvirus; Potyviridae)
Technology Transfer Automated Retrieval System (TEKTRAN)
Bean common mosaic virus (BCMV) and Bean common mosaic necrosis virus (BCMNV) are species within the genus Potyvirus, family Potyviridae and cause some of the most economically important diseases of legume crops worldwide. Both viruses occur essentially wherever bean and cowpea (including Phaseolus...
Intravascular gas in the transplanted kidney: a sign of extensive graft necrosis.
Ishigami, Kousei; Olsen, Kim M; Hammet, Bradley K; Katz, Daniel A; Wu, You Min
We encountered a case of transplanted kidney necrosis, with computed tomography (CT) demonstrating multiple areas of intravascular gas within the allograft. The intravascular gas represented air emboli from gas liberated from fermentation by gas-forming organisms in a perinephric abscess. Arterial bleeding accelerated by the wound infection and the resultant large perinephric hematoma caused renal infarction. Gas-forming infection of transplanted organs is associated with a poor graft outcome, which can present as a fulminant clinical course. Intravascular gas should be distinguished from collecting system gas because the former could represent extensive necrosis of the transplanted kidney. PMID:15290479
Phylogeography of infectious haematopoietic necrosis virus in North America
Kurath, Gael; Garver, Kyle A.; Troyer, Ryan M.; Emmenegger, Eveline J.; Einer-Jensen, Katja; Anderson, Eric D.
Infectious hematopoietic necrosis virus (IHNV) is a rhabdoviral pathogen that infects wild and cultured salmonid fish throughout the Pacific Northwest of North America. IHNV causes severe epidemics in young fish and can cause disease or occur asymptomatically in adults. In a broad survey of 323 IHNV field isolates, sequence analysis of a 303 nucleotide variable region within the glycoprotein gene revealed a maximum nucleotide diversity of 8.6 %, indicating low genetic diversity overall for this virus. Phylogenetic analysis revealed three major virus genogroups, designated U, M and L, which varied in topography and geographical range. Intragenogroup genetic diversity measures indicated that the M genogroup had three- to fourfold more diversity than the other genogroups and suggested relatively rapid evolution of the M genogroup and stasis within the U genogroup. We speculate that factors influencing IHNV evolution may have included ocean migration ranges of their salmonid host populations and anthropogenic effects associated with fish culture.
Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.
Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C
We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. PMID:25948844
Epidemiological characteristics of infectious hematopoietic necrosis virus (IHNV): a review.
Dixon, Peter; Paley, Richard; Alegria-Moran, Raul; Oidtmann, Birgit
Infectious hematopoietic necrosis virus (IHNV, Rhabdoviridae), is the causative agent of infectious hematopoietic necrosis (IHN), a disease notifiable to the World Organisation for Animal Health, and various countries and trading areas (including the European Union). IHNV is an economically important pathogen causing clinical disease and mortalities in a wide variety of salmonid species, including the main salmonid species produced in aquaculture, Atlantic salmon (Salmo salar) and rainbow trout (Oncorhynchus mykiss). We reviewed the scientific literature on IHNV on a range of topics, including geographic distribution; host range; conditions required for infection and clinical disease; minimum infectious dose; subclinical infection; shedding of virus by infected fish; transmission via eggs; diagnostic tests; pathogen load and survival of IHNV in host tissues. This information is required for a range of purposes including import risk assessments; parameterisation of disease models; for surveillance planning; and evaluation of the chances of eradication of the pathogen to name just a few. The review focuses on issues that are of relevance for the European context, but many of the data summarised have relevance to IHN globally. Examples for application of the information is presented and data gaps highlighted. PMID:27287024
Immunity to nervous necrosis virus infections of orange-spotted grouper (Epinephelus coioides) by vaccination with virus-like particles.
Lin, Kebing; Zhu, Zhihuang; Ge, Hui; Zheng, Leyun; Huang, Zhongchi; Wu, Shuiqing
Nervous necrosis virus (NNV) is a kind of the betanodaviruses, which can cause viral nervous necrosis (VNN) and massive mortality in larval and juvenile stages of orange-spotted grouper (Epinephelus coioides). Due to the lack of viral genomes, virus-like particles (VLPs) are considered as one of the most promising candidates in vaccine study to control this disease. In this study, a type of VLPs, which was engineered on the basis of orange-spotted grouper nervous necrosis virus (OGNNV), was produced from prokaryotes. They possessed the similar structure and size to the native NNV. In addition, synthetic oligodeoxynucleotide (ODN) containing CpG motif was added in vaccines, and the expression patterns of several genes were analyzed after injecting with VLP and VLP with adjuvant (VA) to assess the regulation effect of vaccine for inducing immune responses. RT-PCR assays showed that six related genes in healthy tissues were ubiquitously expressed in all nine tested tissues. The vaccine alone was able to enhance the expression of genes, including MHCIa, MyD88, TLR3, TLR9 and TLR22 after vaccination, indicating that the vaccine was able to induce immune response in grouper. In liver, spleen and kidney, the gene expressions of VA group were all significantly higher than that of VLP group at 72 h post-stimulation, showing that the fish of VA challenge group obtained the longer-lasting protective immunity and resistance to pathogen challenge than that of VLP group. The data indicated that the efficacy of vaccine could be further enhanced by CpG ODN after vaccination and provided the reference for the development of future viral vaccine in grouper. PMID:27394969
Vaccinia Virus Induces Programmed Necrosis in Ovarian Cancer Cells
Whilding, Lynsey M; Archibald, Kyra M; Kulbe, Hagen; Balkwill, Frances R; Öberg, Daniel; McNeish, Iain A
The mechanisms by which oncolytic vaccinia virus induces tumor cell death are poorly understood. We have evaluated cell death pathways following infection of ovarian cancer cells with both wild-type and thymidine kinase-deleted (dTK) Lister strain vaccinia. We show that death does not rely upon classical apoptosis despite the appearances of some limited apoptotic features, including phosphatidylserine externalization and appearance of sub-G1 DNA populations. Vaccinia infection induces marked lipidation of LC3 proteins, but there is no general activation of the autophagic process and cell death does not rely upon autophagy induction. We show that vaccinia induces necrotic morphology on transmission electron microscopy, accompanied by marked by reductions in intracellular adenosine triphosphate, altered mitochondrial metabolism, and release of high mobility group box 1 (HMGB1) protein. This necrotic cell death appears regulated, as infection induces formation of a receptor interacting protein (RIP1)/caspase-8 complex. In addition, pharmacological inhibition of both RIP1 and substrates downstream of RIP1, including MLKL, significantly attenuate cell death. Blockade of TNF-α, however, does not alter virus efficacy, suggesting that necrosis does not result from autocrine cytokine release. Overall, these results show that, in ovarian cancer cells, vaccinia virus causes necrotic cell death that is mediated through a programmed series of events. PMID:23985697
Technology Transfer Automated Retrieval System (TEKTRAN)
An outbreak of virus symptoms in the San Juan Valley of the southeastern part of the Dominican Republic during the 1999/2000 dry bean production season was studied. The virus was determined by USDA-ARS at Prosser, WA, to be the NL-8 strain of bean common mosaic necrosis virus. The virus was observed...
Bean Common Mosaic Virus and Bean Common Mosaic Necrosis Virus: Relationships, Biology, and Prospects for Control.
Worrall, Elizabeth A; Wamonje, Francis O; Mukeshimana, Gerardine; Harvey, Jagger J W; Carr, John P; Mitter, Neena
The closely related potyviruses Bean common mosaic virus (BCMV) and Bean common mosaic necrosis virus (BCMNV) are major constraints on common bean (Phaseolus vulgaris) production. Crop losses caused by BCMV and BCMNV impact severely not only on commercial scale cultivation of this high-value crop but also on production by smallholder farmers in the developing world, where bean serves as a key source of dietary protein and mineral nutrition. In many parts of the world, progress has been made in combating BCMV through breeding bean varieties possessing the I gene, a dominant gene conferring resistance to most BCMV strains. However, in Africa, and in particular in Central and East Africa, BCMNV is endemic and this presents a serious problem for deployment of the I gene because this virus triggers systemic necrosis (black root disease) in plants possessing this resistance gene. Information on these two important viruses is scattered throughout the literature from 1917 onward, and although reviews on resistance to BCMV and BCMNV exist, there is currently no comprehensive review on the biology and taxonomy of BCMV and BCMNV. In this chapter, we discuss the current state of our knowledge of these two potyviruses including fundamental aspects of classification and phylogeny, molecular biology, host interactions, transmission through seed and by aphid vectors, geographic distribution, as well as current and future prospects for the control of these important viruses. PMID:26111585
Virulence and serological studies of recombinant infectious hematopoietic necrosis virus (IHNV) in rainbow trout.
Wang, C; Lian, G H; Zhao, L L; Wu, Y; Li, Y J; Tang, L J; Qiao, X Y; Jiang, Y P; Liu, M
Infectious hematopoietic necrosis virus is a highly contagious disease of juvenile salmonid species. From the IHNV HLJ-09 isolated in China, two recombinant viruses were generated by reverse genetics using the RNA polymerase II transcription system. The recombinant viruses were confirmed by RT-PCR, indirect immunofluorescence assay and electron microscopy. They were referred to as rIHNV HLJ-09 and rIHNV-EGFP. rIHNV HLJ-09 and rIHNV-EGFP could stably replicate in EPC cell lines and had the same cellular tropism as wtIHNV HLJ-09. But the titer of rIHNV-EGFP was significantly lower than rIHNV HLJ-09 and wtIHNV HLJ-09. rIHNV-EGFP strain could express EGFP stably at least in 20 passages, and the fluorescence could be observed clearly. To assess the virulence and pathogenicity of the recombinant viruses in vivo, juvenile rainbow trout were challenged by intraperitoneal injection with 20μl of rIHNV HLJ-09, rIHNV-EGFP or wtIHNV HLJ-09 (1×10(6)pfuml(-1)). Fish challenged with rIHNV HLJ-09 and wtIHNV HLJ-09 exhibited clinical signs typical of IHN disease and both produced 90% cumulative percent mortality, whlie rIHNV-EGFP produced only 5%. Pathological sectioning results showed that the tissues (liver, kidney, heart muscle, back muscle) of the fish infected with rIHNV HLJ-09 exhibited pathological changes, with the exception of cerebral neurons and the cheek. However, no lesions of liver, kidney, heart, muscle, brain in rainbow trout of rIHNV-EGFP or the control group were observed. Indirect ELISA results showed that a high level of serum antibody was detected in the experimental fish challenged with rIHNV HLJ-09, just as the same as wtIHNV HLJ-09, while a lower titer was detecred in the fish infected with rIHNV-EGFP. This indicated that the recombinant viruses could induce humoral immune response in the experimental fish. The recombinant viruses had unique genetic tags and could be used for genetic engineering, laying new ground for further investigation of IHNV
Complete Nucleotide Sequence of an Isolate of Coleus vein necrosis virus from Verbena
Technology Transfer Automated Retrieval System (TEKTRAN)
A plant of 'Taylor Town Red' verbena exhibiting mottling, necrosis and low vigor was tested for the presence of viruses by extracting double-stranded RNA which is indicative of infection with an RNA virus. The dsRNA was cloned and sequenced and a novel carlavirus identified. The new virus was dete...
Efficacy of certain disinfectants against infectious pancreatic necrosis virus
Elliott, Diane G.; Amend, Donald F.
The virucidal properties of iodophor, chlorine (sodium hypochlorite), formalin, thimerosal (organic mercurial compound), malachite green, and acriflavine were tested on infectious pancreatic necrosis virus (IPNV). Iodine and chlorine showed good activity, but efficacy depended on the concentration of virus, the presence of organic matter (calf serum), and water pH. Water hardness (0-300 mg 1−1 as CaCO3) did not affect virucidal activity. In a 5 min exposure, 4 mg 1−1available iodine inactivated 103.9 TCID50 m1−1 IPNV but 16 mg 1−1 iodine were needed for inactivation of 106.3TCID50m1−1. The addition of 0-5% calf serum significantly reduced the iodine concentration and the virucidal activity. In comparison, 4 mg 1−1 chlorine were needed to inactivate 1046 TCID50 m1−1 IPNV in 5 min. However, the addition of 0-07 % serum greatly reduced the chlorine concentration and extended the virucidal contact time to 30 min or more. IPNV at 106.3 TCID60 m1−1 was not inactivated by exposures for 60 min to 0-2% formalin, 10 min to 0-2% thimerosal, 60 min to 5 mg 1−1 malachite green, or 20 min to 500 mg 1−1 acriflavine. However, acriflavine at 0-5 mg 1−1 in cell culture media prevented the development of cytopathology caused by IPNV and may be useful in the treatment of the disease.
Immunomagnetic reduction assay for nervous necrosis virus extracted from groupers.
Lu, M W; Yang, S Y; Horng, H E; Yang, C C; Chieh, J J; Hong, Y W; Hong, C Y; Yang, H C; Wu, J L
Nervous necrosis virus (NNV) is the cause of viral nervous disease, which is a serious constraint on production for grouper aquaculture. Real-time PCR is commonly used to detect and quantify NNV, has the disadvantages of being expensive and technically demanding. In this study, an immunomagnetic reduction (IMR) assay was developed as a rapid and cost-effective alternative to real-time PCR. This method used magnetic nanoparticles conjugated with antibodies specific for viral surface antigens to detect NNV in grouper tissue samples. The association of NNV with the antibody-conjugated magnetic particles resulted in a reduction in magnetic signal, which was strongly correlated with the concentration of NNV, as determined by real-time PCR. Grouper larvae were prepared for testing using a viral extraction buffer which provided a rapid, 15-min method of extracting viral antigens and had an extraction efficiency of higher than 80%. In addition, this study proposes using magnetic nanoparticles as labeling markers and as an assaying reagent for NNV. The magnetic nanoparticles are functionalized with antibodies against the viral surface of NNV and are able to associate specifically with NNV. The reduction of the magnetic signals comes from the association between magnetic particles and NNV, and relates to the concentration of NNV. The results show that the detected concentrations of NNV are highly correlated to those detected by real-time PCR. PMID:22335935
Protein expression strategies in Tobacco necrosis virus-D.
Chkuaseli, Tamari; Newburn, Laura R; Bakhshinyan, David; White, K Andrew
Tobacco necrosis virus (TNV-D) has a plus-strand RNA genome that is neither 5' capped nor 3' poly-adenylated. Instead, it utilizes a 3' cap-independent translational enhancer (3'CITE) located in its 3' untranslated region (UTR) for translation of its proteins. We have examined the protein expression strategies used by TNV-D and our results indicate that: (i) a base pairing interaction between conserved ACCA and UGGU motifs in the genomic 5'UTR and 3'CITE, respectively, is not required for efficient plant cell infection, (ii) similar potential 5'UTR-3'CITE interactions in the two viral subgenomic mRNAs are not needed for efficient translation of viral proteins in vitro, (iii) a small amount of capsid protein is translated from the viral genome by a largely 3'CITE-independent mechanism, (iv) the larger of two possible forms of capsid protein is efficiently translated, and (v) p7b is translated from subgenomic mRNA1 by a leaky scanning mechanism. PMID:26402375
Acute retinal necrosis secondary to herpes simplex virus type 2 with preexisting chorioretinal scarring.
Moesen, Ingemarie; Khemka, Sneh; Ayliffe, William
Acute retinal necrosis in children is a devastating disease that requires early diagnosis and treatment. The authors describe a rarely reported case of bilateral acute retinal necrosis in a child caused by neonatal herpes simplex virus type 2, where the presence of previous chorioretinal scarring made diagnosis challenging. PMID:18286969
A strain of Clover yellow vein virus that causes severe pod necrosis disease in snap bean
Technology Transfer Automated Retrieval System (TEKTRAN)
Since 2000, the soybean aphid (Aphis glycines) has been associated with severe virus epidemics in snap bean (Phaseolus vulgaris) in the upper Midwestern states, New York, and Ontario, Canada. The causal agent of a disease causing severe mosaic, apical necrosis stunting and extensive pod necrosis wa...
Infectious Pancreatic Necrosis Virus Causing Clinical and Subclinical Infections in Atlantic Salmon Have Different Genetic Fingerprints
Mutoloki, Stephen; Jøssund, Trude B.; Ritchie, Gordon; Munang'andu, Hetron M.; Evensen, Øystein
Infectious pancreatic necrosis virus (IPNV) is the causative agent of IPN, an important disease of salmonids. IPNV infections result in either sub-clinical or overt disease and the basis of this difference is not well-understood. The objective of the present study was to determine the VP2 gene of the virus associated with the different forms of clinical manifestation. Groups of Atlantic salmon (Salmo salar L.) reared in farms located in different IPN disease pressures were monitored from brood stock until grow-out over a 3 year period. Hatcheries A1 and B1 as well as cooperating seawater farms were located in a low disease risk area while hatcheries A2 and B2 as well as their cooperating seawater farms were in high IPN risk areas. Samples including eggs, milt, whole fry, kidney depending on the stage of production were collected during outbreaks or in apparently healthy populations where no outbreaks occurred. The virus was re-isolated in CHSE cells and the VP2 gene amplified by RT-PCR followed by sequencing. During the freshwater stage, there were no disease outbreaks at hatcheries A1, A2, and B1 (except in one fish group that originated from hatchery B2), although IPNV was isolated from some of the fish groups at all 3 hatcheries. By contrast, all fish groups at hatchery B2 suffered IPN outbreaks. In seawater, only groups of fish originating from hatchery A1 had no IPN outbreaks albeit virus being isolated from the fish. On the other hand, fish originating from hatcheries A2, B1, and B2 experienced outbreaks in seawater. The VP2 amino acid fingerprint of the virus associated with subclinical infections from A1 and co-operating seawater sites was V64A137P217T221A247N252S281D282E319. By contrast, all virus isolates associated with clinical infections had the motif I64T137T217A221T247V252T281N282A319, where underlined amino acids represent the avirulent and highly virulent motif, respectively. Phylogenetic analysis of amino acid sequences showed 2 clades, one of
Retention of infectious haematopoietic necrosis virus infectivity in fish tissue homogenates and fluids stored at three temperatures.
Burke, J.; Mulcahy, D.
Pools of brain, kidney, spleen, liver and gut tissues from several rainbow trout, Salmo gairdneri Richardson, and whole sockeye salmon, Oncorhynchus nerka (Walbaum), fry were homogenized with a known amount of infectious haematopoietic necrosis virus (IHNV). Virus was also added to ovarian fluids and sera pooled from several rainbow trout. The plaque assay was used to determine the retention of IHNV infectivity after different storage periods at 20°C, 4°C and —20°C. The work was used to evaluate homogenization as a remote field treatment of IHNV samples before shipment to the laboratory. Maintenance of viral infectivity varied widely among different homogenates and fluids. For short-term storage, 4°C was generally the most efficient temperature for preserving infectious virus in ovarian fluids, Sera and homogenates of eggs, spleen, whole fry and brain, while infectivity was most efficiently preserved in kidney and liver homogenates by storage at −20°C. Infectious virus was not detected in any sample stored for one year at −20°C. Variations in retention of viral infectivity make homogenization of samples in the field followed by transfer to the laboratory unacceptable.
Tissue tropism of nervous necrosis virus (NNV) in Atlantic cod, Gadus morhua L., after intraperitoneal challenge with a virus isolate from diseased Atlantic halibut, Hippoglossus hippoglossus (L.).
Korsnes, K; Karlsbakk, E; Devold, M; Nerland, A H; Nylund, A
Atlantic cod, Gadus morhua, averaging 100 g, were experimentally challenged by intraperitoneal injection of nervous necrosis virus (NNV) originating from Atlantic halibut. Cod tissues, including blood, gill, pectoral fin, barbel, ventricle, atrium, spleen, liver, lateral line (including muscle tissue), eye (retina) and brain, were sampled at day 25 and 130 and investigated by real-time RT-PCR for the presence of NNV. Relative quantifications at day 130 were calculated using the 2(-DeltaDeltaCt) method. Immunosuppression by injection of prednisolone-acetate was introduced for a 30-day period, and tissue sampled at day 180 and relative quantification estimated. No mortality or clinical signs of disease were observed in the challenged group. The challenge resulted in detection of NNV in blood, spleen, kidney, liver, heart atrium and heart ventricle at day 25, and by the end of the experiment NNV showed a clear increase in brain and retina, suggesting these to be the primary tissues for viral replication. There was no increase in the relative amount of NNV in blood, atrium, ventricle, spleen, liver and kidney. Corticosteroid implants resulted in a weak increase in virus RNA in spleen, kidney, liver and brain. These findings suggest that Atlantic cod is susceptible to infection with NNV from halibut. The observed tissue tropism patterns suggest an initial viraemic phase, followed by neurotrophy. Head-kidney is the best tissue identified for possible NNV detection by non-lethal biopsy, but detection was not possible in all injected fish. PMID:19500207
Persistent infections with infectious pancreatic necrosis virus (IPNV) of different virulence in Atlantic salmon, Salmo salar L.
Julin, K; Johansen, L-H; Sommer, A-I; Jørgensen, J B
Infectious pancreatic necrosis virus (IPNV) is a prevalent pathogen in fish worldwide. The virus causes substantial mortality in Atlantic salmon juveniles and smolts when transferred to sea water and persistent infection in surviving fish after disease outbreaks. Here, we have investigated the occurrence of the virus as well as the innate immune marker Mx in the head kidney (HK) of Atlantic salmon throughout an experimental challenge covering both a fresh and a seawater phase. The fish were challenged with a high (HV) and low virulence (LV) IPNV. Both isolates caused mortality due to reactivation of the virus after transfer to sea water. In the freshwater phase, higher levels of virus transcripts were detected in the HK of fish infected with LV IPNV compared to HV, suggesting that the HV isolate is able to limit its own replication to a level where the innate immune system is not alerted. Further, ex vivoHK leucocytes derived from fish infected with the two isolates were stimulated with CpG DNA. Significantly, higher IFN levels were found in the LV compared to the HV group in the freshwater phase. This suggests that the viruses attenuate the antiviral host immune response at different levels which may contribute to the observed differences in disease outcome. PMID:25557127
Comprehensive gene expression profiling following DNA vaccination of rainbow trout against infectious hematopoietic necrosis virus
Purcell, Maureen K.; Nichols, Krista M.; Winton, James R.; Kurath, Gael; Thorgaard, Gary H.; Wheeler, Paul; Hansen, John D.; Herwig, Russell P.; Park, Linda K.
The DNA vaccine based on the glycoprotein gene of Infectious hematopoietic necrosis virus induces a non-specific anti-viral immune response and long-term specific immunity against IHNV. This study characterized gene expression responses associated with the early anti-viral response. Homozygous rainbow trout were injected intra-muscularly (I.M.) with vector DNA or the IHNV DNA vaccine. Gene expression in muscle tissue (I.M. site) was evaluated using a 16,008 feature salmon cDNA microarray. Eighty different genes were significantly modulated in the vector DNA group while 910 genes were modulated in the IHNV DNA vaccinate group relative to control group. Quantitative reverse-transcriptase PCR was used to examine expression of selected immune genes at the I.M. site and in other secondary tissues. In the localized response (I.M. site), the magnitudes of gene expression changes were much greater in the vaccinate group relative to the vector DNA group for the majority of genes analyzed. At secondary systemic sites (e.g. gill, kidney and spleen), type I IFN-related genes were up-regulated in only the IHNV DNA vaccinated group. The results presented here suggest that the IHNV DNA vaccine induces up-regulation of the type I IFN system across multiple tissues, which is the functional basis of early anti-viral immunity.
... your provider. Alternative Names Necrosis - renal papillae; Renal medullary necrosis Images Kidney anatomy Kidney - blood and urine flow References Ruggenenti P, Cravedi P, Remuzzi G. Microvascular and macrovascular diseases of the kidney. In: Taal MW, Chertow GM, ...
Transcriptome analysis of rainbow trout infected with high and low virulence strains of Infectious hematopoietic necrosis virus
Purcell, Maureen K.; Marjara, Inderjit Singh; Batts, William; Kurath, Gael; Hansen, John D.
There are three main genetic lineages or genogroups of Infectious hematopoietic necrosis virus (IHNV) in N. America. Strains representing the M genogroup are more virulent in rainbow trout relative to the U genogroup. In this study, we used microarray analysis to evaluate potential mechanisms responsible for host-specific virulence in rainbow trout that were given intraperitoneal injections of buffer or a representative M or U type virus strain. Reverse transcriptase quantitative PCR (RT-qPCR) was used to assess viral load and gene expression of select immune genes. Viral load was significantly higher in trout infected with the M virus starting at 24 h post-infection (p.i.) and continuing until 72 h p.i. Microarray analysis of the 48 h time point revealed 153 up-regulated and 248 down-regulated features in response to M virus infection but only 62 up-regulated and 49 down-regulated features following U virus infection. Translation and transcription features were among the most frequent down-regulated features in response to M virus infection and may be associated with the host cell shutoff phenomenon. A greater host cell shutoff response by the M virus may facilitate subversion of the host cell transcriptional machinery and enhance viral replication, suggesting the M virus may be better optimized to manipulate the rainbow trout transcriptional and translational machinery. Anti-viral associated features were the most commonly up-regulated features. A common set of features were up-regulated in both the M and U infection groups, but were induced to a higher magnitude in the M infection group. Gene expression of the anti-viral genes Mx-1 and Vig-1 was correlated but not entirely dependent on viral load in the anterior kidney. Slower replication of the U virus may allow the host more time to induce protective anti-viral immune mechanisms.
Tumor Necrosis Factor Alpha Promoter Polymorphism and Severity of Acute Kidney Injury
Susantitaphong, Paweena; Perianayagam, Mary C.; Tighiouart, Hocine; Liangos, Orfeas; Bonventre, Joseph V.; Jaber, Bertrand L.
Background Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI). Methods We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, α-GST, and π-GST) markers, in 262 hospitalized adults. Results In unadjusted analyses, compared with the GG genotype, the TNFA GA and AA genotype groups tended to have higher enrollment (p = 0.08), peak (p = 0.004), and discharge (p = 0.004) serum creatinine levels, and the AA genotype tended to have a higher enrollment serum cystatin C level (p = 0.04). Compared with the GG genotype, the TNFA GA and AA genotype groups tended to have a higher urinary KIM-1 level (p = 0.03), and the AA genotype group tended to have a higher urinary π-GST level (p = 0.03). After adjustment for sex, race, age, baseline estimated glomerular filtration rate, sepsis, and dialysis requirement, compared with the GG genotype, the TNFA minor A-allele group had a higher peak serum creatinine of 1.03 mg/dl (0.43, 1.63; p = 0.001) and a higher urinary KIM-1 (relative ratio: 1.73; 95% CI: 1.16, 2.59; p = 0.008). The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis. Conclusions The TNFA rs1800629 gene polymorphism is associated with markers of kidney disease severity and distant organ dysfunction among patients with AKI. Larger studies are needed to confirm these relationships. PMID:23796916
Kinetics of viral load and erythrocytic inclusion body formation in pacific herring artificially infected with erythrocytic necrosis virus
Glenn, Jolene A.; Emmenegger, Eveline J.; Grady, Courtney A.; Roon, Sean R.; Gregg, Jacob L.; Conway, Carla M.; Winton, James R.; Hershberger, Paul K.
Viral erythrocytic necrosis (VEN) is a condition that affects marine and anadromous fish species, including herrings and salmonids, in the Atlantic and Pacific oceans. Infection is frequently associated with severe anemia and causes episodic mortality among wild and hatchery fish when accompanied by additional stressors; VEN can be presumptively diagnosed by (1) light microscopic identification of a single characteristic—a round, magenta-colored, 0.8-μm-diameter inclusion body (IB) within the cytoplasm of erythrocytes and their precursors on Giemsa-stained blood films; or (2) observation (via transmission electron microscopy [TEM]) of the causative iridovirus, erythrocytic necrosis virus (ENV), within erythrocytes or their precursors. To better understand the kinetics of VEN, specific-pathogen-free Pacific herring Clupea pallasii were infected with ENV by intraperitoneal injection. At 1, 4, 7, 10, 14, 21, and 28 d postexposure, samples of blood, spleen, and kidney were collected and assessed (1) via light microscopy for the number of intracytoplasmic IBs in blood smears and (2) via TEM for the number of virions within erythrocytes. The mean prevalence of intracytoplasmic IBs in the blood cells increased from 0% at 0–4 d postexposure to 94% at 28 d postexposure. Viral load within circulating red blood cells peaked at 7 d postexposure, fell slightly, and then reached a plateau. However, blood cells observed within the kidney and spleen tissues demonstrated high levels of ENV between 14 and 28 d postexposure. The results indicate that the viral load within erythrocytes does not correlate well with IB prevalence and that the virus can persist in infected fish for more than 28 d.
Technology Transfer Automated Retrieval System (TEKTRAN)
The complete RNA genome of plum bark necrosis stem pitting-associated virus (PBNSPaV) was cloned and sequenced and was determined to be 14, 214 nts long. The genome structure revealed seven major open reading frames (ORFs), and nontranslated regions at the 5' abd 3' ends. PBNSPaV represents the si...
First report of soybean vein necrosis-associated virus in Ohio soybean fields
Technology Transfer Automated Retrieval System (TEKTRAN)
Soybean vein necrosis-associated virus (SVNaV), a newly discovered tospovirus that infects soybean, was first described as widespread in a number of southern and midwestern states, but so far has not been reported in Ohio. Here we describe its occurrence in six different soybean leaf samples collect...
Infectious hematopoietic necrosis virus detected by separation and incubation of cells from salmonid cavity fluid.
Mulcahy, D.; Batts, W.N.
Infectious hematopoietic necrosis (IHN) virus is usually detected by inoculating susceptible cell cultures with cavity ("ovarian") fluid (CF) from spawning females. We identified additional adult carriers of virus in spawning populations of steelhead trout (Salmo gairdneri) and sockeye salmon (Oncorhynchus nerka) by collecting nonerythrocytic cells from CF samples by low-speed centrifugation, culturing the cells for at least 7 d at 15 °C, and then testing the culture medium for virus. Virus appeared in the cultured cells from some samples of CF that remained negative during incubation. In additional samples of CF from these species, the virus titer increased in cultured cells compared with the titer in the original CF sample. With chinook salmon (O.tshawytscha), no negative samples converted to positive during incubation, but the virus titer was retained in incubated CF cells, but not in cell-free CF.
Hepatitis C virus-related kidney disease: an overview.
Kamar, N; Izopet, J; Alric, L; Guilbeaud-Frugier, C; Rostaing, L
Hepatitis C virus (HCV)-infection leads to chronic liver disease, but also to extra-hepatic manifestations, including kidney disease. We provide an overview of HCV-related kidney diseases in non-transplanted and in kidney transplant patients, and their therapies. Membranoproliferative glomerulonephritis, associated with Type 2 cryoglobulinemia, is the predominant Type of HCV-related glomerulonephritis. Membranous glomerulonephritis and focal segmental glomerular sclerosis are less commonly described. HCV infection seems to be linked to Type 2 diabetes mellitus, and might alter the progression of diabetic-related nephropathy. Patients infected by HCV should be annually screened for markers of kidney disease and, similarly, patients with membranoproliferative or membranous glomerulonephritis should be screened for HCV infection. After transplantation, cryoglobulinemia is frequent and is associated with HCV markers. HCV-related kidney disease requires specific treatment. In non-kidney-transplant patients, treatment relies on either only anti-HCV therapy in cases of moderate renal disease, or combined anti-viral and immunosuppressive therapies in cases of severe renal disease, i.e., nephrotic syndrome and/or progressive renal failure, and in diseases that are refractory to anti-HCV therapy. In kidney transplant patients, ribavirin monotherapy could be used cautiously, whereas rituximab might be a treatment of choice in the presence of cryoglobulinemia. In liver-transplant patients, in addition to anti-HCV therapy, rituximab might be also used. PMID:18397713
Genotyping of Korean isolates of infectious hematopoietic necrosis virus (IHNV) based on the glycoprotein gene
Kim, W.-S.; Oh, M.-J.; Nishizawa, T.; Park, J.-W.; Kurath, G.; Yoshimizu, M.
Glycoprotein (G) gene nucleotide sequences of four Korean isolates of infectious hematopoietic necrosis virus (IHNV) were analyzed to evaluate their genetic relatedness to worldwide isolates. All Korean isolates were closely related to Japanese isolates of genogroup JRt rather than to those of North American and European genogroups. It is believed that Korean IHNV has been most likely introduced from Japan to Korea by the movement of contaminated fish eggs. Among the Korean isolates, phylogenetically distinct virus types were obtained from sites north and south of a large mountain range, suggesting the possibility of more than one introduction of virus from Japan. ?? 2007 Springer-Verlag.
Detection of infectious haematopoietic necrosis virus in river water and demonstration of waterborne transmission
Mulcahy, D.; Pascho, R.J.; Jenes, C.K.
In a study of the possible role of waterborne infectious haematopoietic necrosis virus in transmission of the disease among spawning sockeye salmon, Oncorhynchus nerka (Walbaum), both infection rates and virus titres were higher in fish held at high density in a side channel than in fish in the adjacent river. Virus was never isolated from river water, but was found in water from the side channel at levels ranging from 32.5 to 1600 plaque-forming units (p.f.u.)/ml. Uninfected yearling sockeye salmon held in a box in the side channel developed localized gill infections with IHN virus. The disease did not progress to the viscera until a threshold titre of about 105 p.f.u./g was reached in the gill. The effectiveness of the gill as a barrier limiting development of systemic infections means that waterborne IHN virus probably does not greatly increase the infection rate in a sockeye salmon population during spawning.
Occurrence of different types of infectious hematopoietic necrosis virus in fish.
Hsu, Y L; Engelking, H M; Leong, J C
The virion protein patterns of 71 isolates of infectious hematopoietic necrosis virus (IHNV) from the Pacific Northwest were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [35S]-methionine-labeled virus. This analysis led to the classification of these virus isolates into four or more types. Type 1 virus was characterized by a nucleocapsid protein with an approximate molecular weight of 40,500. Type 2 and type 3 viruses have nucleocapsid proteins with molecular weights of 42,800 and 43,250, respectively. Type 2 virus was responsible for the recent epizootics of IHNV among fish in the lower Columbia River. The California IHNV isolates were type 3 with the exception of some of those isolated from fish at the Coleman Hatchery on the Sacramento River. These Coleman Hatchery isolates belonged to a type 4 virus group characterized by a larger glycoprotein of approximately 70,000 molecular weight. All other viruses examined had glycoproteins of 67,000 molecular weight. The "type 5" virus isolates were grouped together because they were not sufficiently distinct to warrant classification into a separate type. These findings have been useful in determining that a particular virus type is characteristic for a geographic area and will infect many different salmonid species in that area and the same type isolated from parental fish is responsible for the subsequent outbreak of the diseases in progeny. Images PMID:3789723
First evidence of infectious hematopoietic necrosis virus (IHNV) in the Netherlands.
Haenen, O L M; Schuetze, H; Cieslak, M; Oldenburg, S; Spierenburg, M A H; Roozenburg-Hengst, I; Voorbergen-Laarman, M; Engelsma, M Y; Olesen, N J
In spring 2008, infectious hematopoietic necrosis virus (IHNV) was detected for the first time in the Netherlands. The virus was isolated from rainbow trout, Oncorhynchus mykiss (Walbaum), from a put-and-take fishery with angling ponds. IHNV is the causative agent of a serious fish disease, infectious hematopoietic necrosis (IHN). From 2008 to 2011, we diagnosed eight IHNV infections in rainbow trout originating from six put-and-take fisheries (symptomatic and asymptomatic fish), and four IHNV infections from three rainbow trout farms (of which two were co-infected by infectious pancreatic necrosis virus, IPNV), at water temperatures between 5 and 15 °C. At least one farm delivered trout to four of these eight IHNV-positive farms. Mortalities related to IHNV were mostly <40%, but increased to nearly 100% in case of IHNV and IPNV co-infection. Subsequent phylogenetic analysis revealed that these 12 isolates clustered into two different monophyletic groups within the European IHNV genogroup E. One of these two groups indicates a virus-introduction event by a German trout import, whereas the second group indicates that IHNV was already (several years) in the Netherlands before its discovery in 2008. PMID:26763082
Infectious haematopoietic necrosis virus genogroup-specific virulence mechanisms in sockeye salmon, Oncorhynchus nerka (Walbaum), from Redfish Lake, Idaho
Purcell, M.K.; Garver, K.A.; Conway, C.; Elliott, D.G.; Kurath, G.
Characterization of infectious haematopoietic necrosis virus (IHNV) field isolates from North America has established three main genogroups (U, M and L) that differ in host-specific virulence. In sockeye salmon, Oncorhynchus nerka, the U genogroup is highly virulent, whereas the M genogroup is nearly non-pathogenic. In this study, we sought to characterize the virus-host dynamics that contribute to genogroup-specific virulence in a captive stock of sockeye salmon from Redfish Lake in Idaho. Juvenile sockeye salmon were challenged by immersion and injection with either a representative U or M viral strain and sampled periodically until 14 days post-infection (p.i.). Fish challenged with each strain had positive viral titre by day 3, regardless of challenge route, but the fish exposed to the M genogroup virus had significantly lower virus titres than fish exposed to the U genogroup virus. Gene expression analysis by quantitative reverse transcriptase PCR was used to simultaneously assess viral load and host interferon (IFN) response in the anterior kidney. Viral load was significantly higher in the U-challenged fish relative to M-challenged fish. Both viruses induced expression of the IFN-stimulated genes (ISGs), but expression was usually significantly lower in the M-challenged group, particularly at later time points (7 and 14 days p.i.). However, ISG expression was comparable with 3 days post-immersion challenge despite a significant difference in viral load. Our data indicated that the M genogroup virus entered the host, replicated and spread in the sockeye salmon tissues, but to a lesser extent than the U genogroup. Both virus types induced a host IFN response, but the high virulence strain (U) continued to replicate in the presence of this response, whereas the low virulence strain (M) was cleared below detectable levels. We hypothesize that high virulence is associated with early in vivo replication allowing the virus to achieve a threshold level, which the
Survival of the salmonid viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV) in ozonated, chlorinated, and Untreated waters
Wedemeyer, Gary A.; Nelson, Nancy C.; Smith, Cathy A.
Ozone and chlorine inactivation curves were determined in three water types at 10 °C for the fish pathogenic viruses infectious hematopoietic necrosis (IHNV) and infectious pancreatic necrosis (IPNV). In phosphate-buffered, distilled water (PBDW) an ozone dose of 0.01 mg/L for 30 or 60 s inactivated IHNV or IPNV, respectively, suspended at a tissue culture 50% infective dose (TCID50) of 104–105/mL. In hard (120 mg/L as CaCO3) and soft water (30 mg/L) lake waters, an ozone application rate of 70 mg∙h−1∙L−1 for 10 min destroyed IHNV. IPNV inactivation in hard water required 90 mg∙O3∙h−1∙L−1 for 10 min but only a 30-s contact time in soft water. The IPNV was also somewhat more resistant to chlorine. In PBDW, a residual of 0.1 mg/L with contact times of 30 and 60 s, respectively, destroyed IHNV and IPNV. In soft lake water IHNV was destroyed within 5 min at 0.5 mg/L, while in hard water a 10-min contact time was required. For IPNV disinfection in soft water, 0.2 mg/L for 10 min was sufficient but this chlorine residual had essentially no effect on IPNV in hard water. Increasing this dose to 0.7 mg/L destroyed IPNV in hard water within 2 min. In untreated waters, IPNV was stable for at least 8 wk in either distilled, soft, or hard lake waters. However, IHNV survived only about 2 wk in distilled and 7 wk in the soft or hard lake waters. We suggest the serious consideration of ozone as a fish disease control agent. Key words: ozone, chlorine disinfection, fish pathogens, viruses
Engineered single-chain variable fragment antibody for immunodiagnosis of groundnut bud necrosis virus infection.
Maheshwari, Yogita; Vijayanandraj, S; Jain, R K; Mandal, Bikash
Few studies have been done on engineered antibodies for diagnosis of tospovirus infections. The present study was undertaken to develop a single-chain variable fragment (scFv) for specific diagnosis of infection by groundnut bud necrosis virus (GBNV), the most prevalent serogroup IV tospovirus in India. Heavy chain (372 nucleotide [nt]) and light chain (363 nt) variable region clones obtained from a hybridoma were used to make an scFv construct that expressed a ~29-kDa protein in E. coli. The scFv specifically detected GBNV in field samples of cowpea, groundnut, mung bean, and tomato, and it did not recognize watermelon bud necrosis virus, a close relative of GBNV belonging to tospovirus serogroup IV. This study for the first time demonstrated the application of a functional scFv against a serogroup-IV tospovirus. PMID:25698103
Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus.
Kell, Alison M; Wargo, Andrew R; Kurath, Gael
Viral genotype displacement events are characterized by the replacement of a previously dominant virus genotype by a novel genotype of the same virus species in a given geographic region. We examine here the fitness of three pairs of infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major genotype displacement events in Washington state over the last 30 years to determine whether increased virus fitness correlates with displacement. Fitness was assessed using in vivo assays to measure viral replication in single infection, simultaneous co-infection, and sequential superinfection in the natural host, steelhead trout. In addition, virion stability of each genotype was measured in freshwater and seawater environments at various temperatures. By these methods, we found no correlation between increased viral fitness and displacement in the field. These results suggest that other pressures likely exist in the field with important consequences for IHNV evolution. PMID:25068402
Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus
Kell, Alison M; Wargo, Andrew R; Kurath, Gael
Viral genotype displacement events are characterized by the replacement of a previously dominant virus genotype by a novel genotype of the same virus species in a given geographic region. We examine here the fitness of three pairs of infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major genotype displacement events in Washington state over the last 30 years to determine whether increased virus fitness correlates with displacement. Fitness was assessed using in vivo assays to measure viral replication in single infection, simultaneous co-infection, and sequential superinfection in the natural host, steelhead trout. In addition, virion stability of each genotype was measured in freshwater and seawater environments at various temperatures. By these methods, we found no correlation between increased viral fitness and displacement in the field. These results suggest that other pressures likely exist in the field with important consequences for IHNV evolution. PMID:25068402
Viral fitness does not correlate with three genotype displacement events involving infectious hematopoietic necrosis virus
Kell, Alison M.; Wargo, Andrew R.; Kurath, Gael
Viral genotype displacement events are characterized by the replacement of a previously dominant virus genotype by a novel genotype of the same virus species in a given geographic region. We examine here the fitness of three pairs of infectious hematopoietic necrosis virus (IHNV) genotypes involved in three major genotype displacement events in Washington state over the last 30 years to determine whether increased virus fitness correlates with displacement. Fitness was assessed using in vivo assays to measure viral replication in single infection, simultaneous co-infection, and sequential superinfection in the natural host, steelhead trout. In addition, virion stability of each genotype was measured in freshwater and seawater environments at various temperatures. By these methods, we found no correlation between increased viral fitness and displacement in the field. These results suggest that other pressures likely exist in the field with important consequences for IHNV evolution.
Neutralizing monoclonal antibodies recognize antigenic variants among isolates of infectious hematopoietic necrosis virus
Winton, J.R.; Arakawa, C.N.; Lannan, C.N.; Fryer, J.L.
eutralizing monoclonal antibodies were developed against strains of infectious hematopoietic necrosis virus (IHNV) from steelhead trout Salmo gairdneri in the Deschutes River of Oregon, chinook salmon Oncorhynchus tshawytscha in the Sacramento River of California, and rainbow trout Salmo gairdneri reared in the Hagerman Valley of Idaho, USA. These antibodies were tested for neutralization of 12 IHNV isolates obtained from salmonids in Japan, Alaska, Washington, Oregon, California, and Idaho. The antibodies recognized antigenic variants among the isolates and could be used to separate the viruses into 4 groups. The members of each group tended to be related by geographic area rather than by source host species, virulence, or date of isolation.
Zavyalova, E A; Gulyukin, M I; Carpova, M A; Bogdanova, P D; Droshnev, A E
The infectious pancreatic necrosis (IPN) caused by a non-enveloped virus of the Birnaviridae family is one of the most important loss factors in the salmonid aquaculture. Virus isolation in the sensitive cell cultures has been approved in the Russian Federation as the diagnostic method for determination of IPNV antigen. This work gives the results of the development of the diagnostic test to reveal IPNV using the antigen-bound ELISA (sandwich ELISA). The developed test supplements a new diagnostic method and verifies some disputable results obtained with classical methods. PMID:27145601
Human tumor necrosis factor alpha gene regulation by virus and lipopolysaccharide.
Goldfeld, A E; Doyle, C; Maniatis, T
We have identified a region of the human tumor necrosis factor alpha (TNF-alpha) gene promoter that is necessary for maximal constitutive, virus-induced, and lipopolysaccharide (LPS)-induced transcription. This region contains three sites that match an NF-kappa B binding-site consensus sequence. We show that these three sites specifically bind NF-kappa B in vitro, yet each of these sites can be deleted from the TNF-alpha promoter with little effect on the induction of the gene by virus or LPS. Moreover, when multimers of these three sites are placed upstream from a truncated TNF-alpha promoter, or a heterologous promoter, an increase in the basal level of transcription is observed that is influenced by sequence context and cell type. However, these multimers are not sufficient for virus or LPS induction of either promoter. Thus, unlike other virus- and LPS-inducible promoters that contain NF-kappa B binding sites, these sites from the TNF-alpha promoter are neither required nor sufficient for virus or LPS induction. Comparison of the sequence requirements of virus induction of the human TNF-alpha gene in mouse L929 and P388D1 cells reveals significant differences, indicating that the sequence requirements for virus induction of the gene are cell type-specific. However, the sequences required for virus and LPS induction of the gene in a single cell type, P388D1, overlap. Images PMID:2263628
Antigen detection and apoptosis in Mongolian gerbil's kidney experimentally intraperitoneally infected by swine hepatitis E virus.
Soomro, Majid Hussain; Shi, Ruihan; She, Ruiping; Yang, Yifei; Hu, Fengjiao; Li, Heng
We examined the effect of hepatitis E virus (HEV) on the renal tissue pathogenesis, morphological damages and related molecular mechanisms following swine HEV suspension intraperitoneally inoculation in Mongolian gerbils. The microscopic and ultramicroscopic analyses of kidney tissue structure were carried out at different points after inoculation of HEV. The immunohistochemistry, real-time PCR and Western blot were performed to explore the molecular mechanisms associated with HEV presence in the renal tissues. Real-time PCR revealed that the copies of HEV RNA in the kidney were detected at 7 dpi, and peaked at 14 dpi at a concentration was 7.18 logs g(-1), with detection of HEV ORF2 antigen by immunohistochemistry. Hematoxylin and eosin (HE) staining showed pathological lesions including glomerular atrophy, degeneration, edema and necrosis of renal tubular epithelial cells and Mallory and Sirius red staining indicated the presence of collagen fibers and fibrosis in kidney tissues of inoculated gerbils. Ultrastructural studies of basal membrane of renal tubules demonstrated the rough and uneven with mitochondria swelling and vacuolation in the tissues of HEV inoculated animals. Similarly, significantly higher number of (TUNEL)-positive cells were seen in renal tubule tissues compared to control group. Moreover, immuno histochemical results indicated that significant increase expression of the B-cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), FAS and Caspase-3 in HEV inoculated Mongolian gerbils at each time points. Relative mRNA expression by real-time PCR revealed a significantly higher (P<0.05) mRNA level of BAX, Bcl-2 and caspase-3 transcription in HEV inoculated Mongolian gerbils. Our results demonstrates that activation of mitochondria and Caspase-3 protease might be induced the apoptosis which subsequently cause the necrosis and cell death of renal epithelial cells during acute phase of HEV infection in HEV inoculated Mongolian gerbils. PMID
Arabidopsis TTR1 causes LRR-dependent lethal systemic necrosis, rather than systemic acquired resistance, to Tobacco ringspot virus
Technology Transfer Automated Retrieval System (TEKTRAN)
Most Arabidopsis ecotypes display tolerance to the Tobacco ringspot virus (TRSV), but a subset of Arabidopsis ecotypes, including Estland (Est), develop lethal systemic necrosis (LSN), which differs from the localized hypersensitive responses (HRs) or systemic acquired resistance (SAR) characteristi...
Genetic and serological characterization of chrysanthemum stem necrosis virus, a member of the genus Tospovirus.
Wu, Pei-Ru; Chien, Wan-Chu; Okuda, Mitsuru; Takeshita, Minoru; Yeh, Shyi-Dong; Wang, Yun-Chi; Chen, Tsung-Chi
Chrysanthemum stem necrosis virus (CSNV) is a member of a tentative tospovirus species. In this study, the complete genomic sequence of the Japanese CSNV isolate TcCh07A was determined. The L RNA is 8960 nt long and encodes the 331.0-kDa RNA-dependent RNA polymerase. The M RNA is 4828 nt long and encodes the 34.1-kDa movement protein (NSm) and the 127.7-kDa glycoprotein precursor (Gn/Gc). The S RNA is 2949 nt long and encodes the 52.4-kDa silencing suppressor protein (NSs) and the 29.3-kDa nucleocapsid (N) protein. The N protein of CSNV-TcCh07A was purified from virus-infected plant tissues and used for production of a rabbit polyclonal antiserum (RAs) and a monoclonal antibody (MAb). Results of serological tests by indirect ELISA and western blotting using the prepared RAs and MAb and a previously produced RAs against the N protein of tomato spotted wilt virus (TSWV) indicated that CSNV-TcCh07A, TSWV, tomato chlorotic spot virus, groundnut ringspot virus, alstroemeria necrotic streak virus and impatiens necrotic spot virus are serologically related. PMID:25427981
Capsid is an important determinant for functional complementation of murine leukemia virus and spleen necrosis virus Gag proteins.
Lee, Sook-Kyung; Boyko, Vitaly; Hu, Wei-Shau
In this report, we examined the abilities and requirements of heterologous Gag proteins to functionally complement each other to support viral replication. Two distantly related gammaretroviruses, murine leukemia virus (MLV) and spleen necrosis virus (SNV), were used as a model system because SNV proteins can support MLV vector replication. Using chimeric or mutant Gag proteins that could not efficiently support MLV vector replication, we determined that a homologous capsid (CA) domain was necessary for the functional complementation of MLV and SNV Gag proteins. Findings from the bimolecular fluorescence complementation assay revealed that MLV and SNV Gag proteins were capable of colocalizing and interacting in cells. Taken together, our results indicated that MLV and SNV Gag proteins can interact in cells; however, a homologous CA domain is needed for functional complementation of MLV and SNV Gag proteins to complete virus replication. This requirement of homologous Gag most likely occurs at a postassembly step(s) of the viral replication. PMID:17156810
Morphology of certain viruses of Salmonid Fishes. I. in vitro studies of some viruses causing Hematopoietic Necrosis
Amend, Donald F.; Chambers, Velma C.
An electron microscope study was performed on three virus isolates that caused hematopoietic necrosis in salmonid fishes: infectious hematopoietic necrosis (IHN), Oregon Sockeye Disease (OSD), and Sacramento River Chinook Salmon Disease (SRCD). All three isolates were examined by negative staining of fathead minnow (FHM) monolayer tissue culture concentrates and IHN virus was also examined in thin sections of FHM cells. Viruslike particles were observed in infected tissues, but similar structures were not found in uninfected cultures. All three isolates were bullet-shaped, but oval and truncated forms were also observed. Mean measurements of particles from IHN-virus-infected tissue were 158 × 90 mμ. They consisted of an outer coat 15 mμ thick, a core 60 mμ in diameter, subunits about 5 mμ, and an axial pore about 20 mμ in diameter. These particles also were seen budding from the cytoplasmic membrane. Similar particles from SRCD were 159 × 90 mμ and isolates from OSD were 181 × 91 mμ. The three isolates were morphologically indistinguishable from one another and the greater length of OSD was considered insignificant. IHN, SRCD, and OSD viruses were tentatively placed in the rhabdovirus group, but serological studies are needed to determine if they are antigenically identical or should be included as separate members. Biochemical and physical characteristics of these viruses and a comparison with other salmonid viruses is also discussed.
Responses of cloned rainbow trout Oncorhynchus mykiss to an attenuated strain of infectious hematopoietic necrosis virus.
Ristow, S S; LaPatra, S E; Dixon, R; Pedrow, C R; Shewmaker, W D; Park, J W; Thorgaard, G H
The objective of this work was to examine the response of homozygous clones of rainbow trout to vaccination by an attenuated strain (Nan Scott Lake; NSL) of infectious hematopoietic necrosis virus (IHNV). Adult rainbow trout of the Hot Creek Strain (YY males maintained in a recirculating system at 12 degrees C) were injected 3 times with 10(5) to 10(7) plaque forming units (pfu) of NSL. Intraperitoneal injections were given at Day 0 and at 2 and 4 mo post-infection. All fish were nonlethally bled at monthly intervals for 18 mo. Serum from each fish was analyzed by the complement-dependent neutralization assay and by western blot against purified NSL virus. The highest virus neutralization titers were detected 4 mo after the first injection, and peaked at 1280. When sera were analyzed by western blot, the predominating responses of the serum from immunized fish on the reduced western blot were against M1, a matrix protein of the virus and to a 90 kDa stress protein. The 90 kDa protein was identified by a monoclonal antibody as a stress protein derived from the CHSE-214 cells in which the purified IHN virus was grown and which associates with the virus during purification. PMID:11104067
Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV).
McKenney, Douglas G; Kurath, Gael; Wargo, Andrew R
The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50 values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout. PMID:26752429
Genomics, Molecular Epidemiology and Diagnostics of Infectious hypodermal and hematopoietic necrosis virus.
Rai, Praveen; Safeena, Muhammed P; Krabsetsve, Kjersti; La Fauce, Kathy; Owens, Leigh; Karunasagar, Indrani
Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is one of the major viral pathogens of penaeid shrimps worldwide, which has resulted in severe mortalities of up to 90 % in cultured Penaeus (Litopenaeus) stylirostris from Hawaii and hence designated Penaeus stylirostris densovirus (PstDNV). IHHNV is distributed in shrimp culture facilities worldwide. It causes large economic loss to the shrimp farming industry. Our knowledge about the natural reservoirs of IHHNV is still scarce. Recent studies suggest that there is sufficient sequence variation among the isolates from different locations in Asia, suggesting multiple geographical strains of the virus. Four complete genomes and several partial sequences of the virus are available in the GenBank. Complete genome information would be useful for assessing the specificity of diagnostics for viruses from different geographical areas. Comparisons of complete genome sequences will help us gain insights into point mutations that can affect virulence of the virus. In addition, because of unavailability of shrimp cell lines for culturing IHHNV in vitro, quantification of virus is difficult. The recent progress in research regarding clinical signs, geographical distribution, complete genome sequence and genetic variation, transmission has made it possible to obtain information on IHHNV. A comprehensive understanding of IHHNV infection process, pathogenesis, structural proteins and replication is essential for developing prevention measures. To date, no effective prophylactic measure for IHHNV infection is available for shrimp to reduce its impact. This review provides an overview of key issues regarding IHHNV infection and disease in commercially important shrimp species. PMID:23997444
Characterization of infectious dose and lethal dose of two strains of infectious hematopoietic necrosis virus (IHNV)
McKenney, Douglas; Kurath, Gael; Wargo, Andrew
The ability to infect a host is a key trait of a virus, and differences in infectivity could put one virus at an evolutionary advantage over another. In this study we have quantified the infectivity of two strains of infectious hematopoietic necrosis virus (IHNV) that are known to differ in fitness and virulence. By exposing juvenile rainbow trout (Oncorhynchus mykiss) hosts to a wide range of virus doses, we were able to calculate the infectious dose in terms of ID50 values for the two genotypes. Lethal dose experiments were also conducted to confirm the virulence difference between the two virus genotypes, using a range of virus doses and holding fish either in isolation or in batch so as to calculate LD50values. We found that infectivity is positively correlated with virulence, with the more virulent genotype having higher infectivity. Additionally, infectivity increases more steeply over a short range of doses compared to virulence, which has a shallower increase. We also examined the data using models of virion interaction and found no evidence to suggest that virions have either an antagonistic or a synergistic effect on each other, supporting the independent action hypothesis in the process of IHNV infection of rainbow trout.
Evidence for a carrier state of infectious hematopoietic necrosis virus in chinook salmon Oncorhynchus tshawytscha.
St Hilaire, S; Ribble, C; Traxler, G; Davies, T; Kent, M L
In British Columbia, Canada, infectious hematopoietic necrosis virus (IHNV) is prevalent in wild sockeye salmon Oncorhynchus nerka and has caused disease in seawater net-pen reared Atlantic salmon Salmo salar. In this study, chinook salmon Oncorhynchus tshawytscha experimentally exposed to an isolate of IHNV found in British Columbia became carriers of the virus. When Atlantic salmon were cohabited with these virus-exposed chinook salmon, IHNV was isolated from the Atlantic salmon. Identification of chinook salmon populations that have been exposed to IHNV may be difficult, as virus isolation was successful only in fish that were concurrently infected with either Renibacterium salmoninarum or Piscirickettisia salmonis. Also, IHNV-specific antibodies were detected in only 2 of the 70 fish experimentally exposed to the virus. Two samples collected from chinook salmon exposed to IHNV while at a salt water net-pen site had a seroprevalence of 19 and 22%; however, the inconsistencies between our laboratory and field data suggest that further research is required before we can rely on serological analysis for identifying potential carrier populations. Because of the difficulty in determining the exposure status of populations of chinook salmon, especially if there is no concurrent disease, it may be prudent not to cohabit Atlantic salmon with chinook salmon on a farm if there is any possibility that the latter have been exposed to the virus. PMID:11710551
Characterization of Verbena virus Y, a New Component in the Complex Causing Necrosis in Verbena 'Taylortown Red'
Technology Transfer Automated Retrieval System (TEKTRAN)
A ' Taylortown Red' verbena plant from Michigan showed mottling symptoms that progressed to necrosis as leaves matured. The plant was assayed and was found positive for double-stranded RNA, indicative of virus infection, which was cloned and sequenced. Three viruses were identified: Broad bean wilt ...
Susceptibility of Australian Redfin Perch Perca fluviatilis Experimentally Challenged with Epizootic Hematopoietic Necrosis Virus (EHNV).
Becker, Joy A; Tweedie, Alison; Gilligan, Dean; Asmus, Martin; Whittington, Richard J
The ranavirus epizootic hematopoietic necrosis virus (EHNV) is endemic to Australia and is listed by the Office International des Epizooties. Clinical outbreaks have only been observed in wild populations of Redfin Perch Perca fluviatilis (also known as Eurasian Perch) and farmed populations of Rainbow Trout Oncorhynchus mykiss. The initial outbreaks of EHNV describe all age-classes of Redfin Perch as being susceptible and can lead to epidemic fish kills. Subsequently, experimental challenge studies using either cohabitation with the virus or injection exposures resulted in mixed susceptibilities across various age-groupings of Redfin Perch. We used an experimental bath challenge model to investigate the susceptibility of Redfin Perch collected from areas with and without a history of EHNV outbreaks. The median survival time for fish from Blowering Dam in New South Wales, a zone with a history of EHNV outbreaks, was 35 d, compared with fish from other areas, which had a median survival between 12 and 28 d postexposure. Redfin Perch from Blowering Dam demonstrated an increased mortality associated with epizootic hematopoietic necrosis up to approximately day 14 after exposure, and then there was a significantly reduced risk of mortality until the end of the trial compared with all other fish. Redfin Perch from Blowering Dam had markedly decreased susceptibility to EHNV, and less than 40% became infected following a bath challenge. In contrast, Redfin Perch from neighboring (e.g., Bethungra Dam and Tarcutta Creek) and distant water bodies (e.g., in Western Australia) with no previous history of EHNVdisplayed moderate to high susceptibility when given a bath challenge. Potential factors for the observed changes in the host-pathogen relationship include intense positive selection pressure for resistant fish following epizootic hematopoietic necrosis outbreaks and subsequent attenuation of the virulence of the virus in resistant fish. Received August 22, 2015; accepted
Control of infectious Hematopoietic Necrosis virus disease by elevating the water temperature
Amend, Donald F.
Studies were performed to determine if increasing water temperatures could control infectious hematopoietic necrosis virus (IHN) disease in sockeye salmon (Oncorhynchus nerka). Mortalities could be prevented if the water temperature was raised to at least 18 C within the first 24 hr after infection of the fish and if the fish were maintained at this temperature for 4–6 days. The disease did not recur after the elevated temperature treatment, but the fish would still contract the disease if they were reinfected. Reasons for the protecting action are discussed.
Genetic relatedness of infectious hematopoietic necrosis virus (IHNV) from cultured salmonids in Korea.
Kim, Kwang Il; Cha, Seung Joo; Lee, Chu; Baek, Harim; Hwang, Seong Don; Cho, Mi Young; Jee, Bo Young; Park, Myoung-Ae
Infectious hematopoietic necrosis virus (IHNV; n = 18) was identified in the Korean national surveillance program between February 2013 and April 2015, suggesting that IHNV is a major viral pathogen in cultured salmonids. By phylogeny analysis, we found that the JRt-Nagano and JRt-Shizuoka groups could each be further subdivided into three distinct subtypes. The Korean strains were genetically similar to Japanese isolates, suggesting introduction from Japan. Interestingly, the amino acid sequences of the middle glycoprotein gene show that distinct Korean subtypes have circulated, indicating that the settled IHNVs might be evolved stably in cultured salmonid farm environments. PMID:27255747
Neutralization-resistant variants of infectious hematopoietic necrosis virus have altered virulence and tissue tropism.
Kim, C H; Winton, J R; Leong, J C
Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus that causes an acute disease in salmon and trout. In this study, a correlation between changes in tissue tropism and specific changes in the virus genome appeared to be made by examining four IHNV neutralization-resistant variants (RB-1, RB-2, RB-3, and RB-4) that had been selected with the glycoprotein (G)-specific monoclonal antibody RB/B5. These variants were compared with the parental strain (RB-76) for their virulence and pathogenicity in rainbow trout after waterborne challenge. Variants RB-2, RB-3, and RB-4 were only slightly attenuated and showed distributions of viral antigen in the livers and hematopoietic tissues of infected fish similar to those of the parental strain. Variant RB-1, however, was highly attenuated and the tissue distribution of viral antigen in RB-1-infected fish was markedly different, with more viral antigen in brain tissue. The sequences of the G genes of all four variants and RB-76 were determined. No significant changes were found for the slightly attenuated variants, but RB-1 G had two changes at amino acids 78 and 218 that dramatically altered its predicted secondary structure. These changes are thought to be responsible for the altered tissue tropism of the virus. Thus, IHNV G, like that of rabies virus and vesicular stomatitis virus, plays an integral part in the pathogenesis of viral infection. Images PMID:7525991
Inhibition of Cellular DNA Synthesis in Cells Infected with Infectious Pancreatic Necrosis Virus
Lothrop, David; Nicholson, Bruce L.
In asynchronous RTG-2 cell cultures infected with infectious pancreatic necrosis (IPN) virus, inhibition of cellular DNA synthesis, but not protein synthesis, was detected 5 to 6 h postinfection and was 80 to 90% complete by 7 to 8 h. Inhibition of DNA synthesis was largely abolished by UV irradiation of the virus. Sedimentation analyses of phenol-extracted DNA indicated that native cellular DNA was not degraded during infection. Sedimentation on alkaline sucrose gradients of DNA from cells pulsed with radioactive thymidine for varying periods indicated that elongation of nascent DNA chains proceeded normally in infected cells. These and previous results suggest that IPN virus infection results in a reduction of the number of chromosomal sites active in DNA synthesis but does not affect the rate of polymerization at active sites. Cells synchronized with excess thymidine and hydroxyurea and infected with virus at the time of release from the block demonstrated an inhibition of DNA synthesis 3 h postinfection. Cells infected 4 h prior to release continued to synthesize normal amounts of DNA for 1 to 2 h after release. These results indicated that DNA synthesis in early synthetic phase is relatively insensitive to inhibition by IPN virus. PMID:4852469
In vitro RNA synthesis by infectious pancreatic necrosis virus-associated RNA polymerase.
Mertens, P P; Jamieson, P B; Dobos, P
The presence of an RNA-dependent RNA polymerase was demonstrated in purified infectious pancreatic necrosis virus (IPNV). The enzyme was active in vitro without any pretreatment of the virus. Optimum activity was shown at 30 degrees C, pH 8 and in the presence of 6 mM-magnesium ions. Approx. 50% of the polymerase product remained associated with the dsRNA template of the virions. The remainder was found as extravirion ssRNA broken down to 5S to 7S fragments by virus-associated RNase(s). Although the addition of bentonite considerably reduced the amount of RNA synthesized, it protected the ssRNA product from degradation. This, in turn, permitted the synthesis of small amounts of ssRNA, which when analysed by sucrose gradient centrifugation or polyacrylamide gel electrophoresis behaved identically to the 24S single-stranded virus mRNA produced in infected cells. The virion polymerase was not stimulated by S-adenosyl-L-methionine or the addition of cellular or capped reovirus ssRNA. Several other modifications of the assay system were tried in an attempt to increase 24S RNA synthesis, but with little success. When [3H]uridine-labelled virus was used in the polymerase reaction, some labelled 24S ssRNA was obtained, indicating that in vitro transcription may proceed by a semi-conservative (displacement) mechanism. PMID:6175731
Acute Retinal Necrosis Associated with Epstein-Barr Virus in a Patient Undergoing Immunosuppressive Therapy
Oe, Chiaki; Hiraoka, Miki; Tanaka, Sachie; Ohguro, Hiroshi
Acute retinal necrosis (ARN) is a rapidly progressive and severe retinitis resulting in a poor visual outcome. Infections caused by herpes viruses such as herpes simplex virus (HSV) types 1 and 2 or the varicella zoster virus (VZV) are known to be implicated in the development of ARN. In the present study, an 80-year-old female with ARN was examined. She had been affected with rheumatoid arthritis and had taken methotrexate for over 10 years. Her right eye showed clinical features of ARN, and her left eye showed mild retinitis. The genomic DNA in the aqueous humor and vitreous fluid from her right eye were analyzed by a comprehensive polymerase chain reaction (PCR) assay to screen infectious pathogens including viruses. The Epstein-Barr virus (EBV) was detected from both specimens, but neither HSV or VZV nor cytomegalovirus was detected. She underwent intraocular surgery following systemic corticosteroid and acyclovir applications. However, although the retinitis of her right eye was extinguished, the final visual outcome was blindness due to optic nerve atrophy. There are few reports indicating that EBV is associated with ARN development. The present findings suggest that EBV alone can be the causative agent of ARN. PMID:27194989
Occurrence and genetic typing of infectious hematopoietic necrosis virus in Kamchatka, Russia
Rudakova, S.L.; Kurath, G.; Bochkova, E.V.
Infectious hematopoietic necrosis virus (IHNV) is a well known rhabdoviral pathogen of salmonid fish in North America that has become established in Asia and Europe. On the Pacific coast of Russia, IHNV was first detected in hatchery sockeye from the Kamchatka Peninsula in 2001. Results of virological examinations of over 10 000 wild and cultured salmonid fish from Kamchatka during 1996 to 2005 revealed IHNV in several sockeye salmon Oncorhynchus nerka populations. The virus was isolated from spawning adults and from juveniles undergoing epidemics in both hatchery and wild sockeye populations from the Bolshaya watershed. No virus was detected in 2 other water-sheds, or in species other than sockeye salmon. Genetic typing of 8 virus isolates by seguence analysis of partial glycoprotein and nucleocapsid genes revealed that they were genetically homogeneous and fell within the U genogroup of IHNV. In phylogenetic analyses, the Russian IHNV sequences were indistinguishable from the sequences of North American U genogroup isolates that occur throughout Alaska, British Columbia, Washington, and Oregon. The high similarity, and in some cases identity, between Russian and North American IHNV isolates suggests virus transmission or exposure to a common viral reservoir in the North Pacific Ocean. ?? Inter-Research 2007.
Update on kidney transplantation in human immunodeficiency virus infected recipients.
Nashar, Khaled; Sureshkumar, Kalathil K
Improved survival of human immunodeficiency virus (HIV) infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV(+) donors to HIV(+) recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The first HIV(+) to HIV(+) kidney transplant in the United States and the first HIV(+) to HIV(+) liver transplant in the world were recently performed at the Johns Hopkins University Medical Center. PMID:27458559
Update on kidney transplantation in human immunodeficiency virus infected recipients
Nashar, Khaled; Sureshkumar, Kalathil K
Improved survival of human immunodeficiency virus (HIV) infected patients with chronic kidney disease following the introduction of antiretroviral therapy resulted in the need to revisit the topic of kidney transplantation in these patients. Large cohort studies have demonstrated favorable outcomes and proved that transplantation is a viable therapeutic option. However, HIV-infected recipients had higher rates of rejection. Immunosuppressive therapy did not negatively impact the course of HIV infection. Some of the immunosuppressive drugs used following transplantation exhibit antiretroviral effects. A close collaboration between infectious disease specialists and transplant professionals is mandatory in order to optimize transplantation outcomes in these patients. Transplantation from HIV+ donors to HIV+ recipients has been a subject of intense debate. The HIV Organ Policy Equity act provided a platform to research this area further and to develop guidelines. The first HIV+ to HIV+ kidney transplant in the United States and the first HIV+ to HIV+ liver transplant in the world were recently performed at the Johns Hopkins University Medical Center. PMID:27458559
Chronic kidney disease in human immunodeficiency virus infection.
Fabian, J; Katz, I; Gerntholtz, T; Goetsch, S; Naicker, S
The number of people living with human immunodeficiency virus (HIV) worldwide was estimated to be 39.5 million in 2006, 2.6 million more than in 2004. The manifestations of HIV infection in the kidney are multiple and varied, highlighting the complexity of the disease process. There is a wide spectrum of renal disease that occurs in the course of HIV infection. Biopsy studies reveal varying frequencies of histological patterns. HIV-associated nephropathy (HIVAN) is most common. A biopsy study at Chris Baragwanath Hospital in Soweto, South Africa showed that HIVAN was present in 27% and immune complex disease in 21%. Han et al. studied HIV-positive patients in Durban, South Africa and screened for proteinuria, including microalbuminuria. They found persistent proteinuria in 6%; HIVAN in 21/30 (72.4%) and the prevalence of HIVAN in patients with persistent microalbuminuria was 85.7%. Studies in black patients have shown a higher prevalence of both severe glomerular lesions (focal glomerulosclerosis) and nephrotic range proteinuria with renal dysfunction in the presence of normo-hypotension. There have been no prospective randomised controlled studies with any form of therapy for HIVAN to date. Therapy of HIVAN has included corticosteroids, cyclosporine and antiretroviral therapy (ART). ART appears to be a logical choice in the management of HIV-associated renal disease. Regimens containing protease inhibitors have been shown to be associated with significant slowing of the decline in creatinine clearance. Both peritoneal dialysis and haemodialysis are appropriate treatment modalities for HIV-infected patients with end stage renal disease. The choice of dialysis modality between haemodialysis and peritoneal dialysis is not a factor in predicting survival, if patients are stable on ART. Preliminary short-term data in case reports and small cohorts of liver, kidney, and heart transplant recipients suggest that patient survival rates may be similar to those in HIV
Molecular identification of erythrocytic necrosis virus (ENV) from the blood of Pacific herring (Clupea pallasii)
Emmenegger, Eveline J.; Glenn, Jolene A.; Winton, James R.; Batts, William N.; Gregg, Jacob L.; Hershberger, Paul K.
Viral erythrocytic necrosis (VEN) is a condition affecting the red blood cells of more than 20 species of marine and anadromous fishes in the North Atlantic and North Pacific Oceans. Among populations of Pacific herring (Clupea pallasii) on the west coast of North America the disease causes anemia and elevated mortality in periodic epizootics. Presently, VEN is diagnosed by observation of typical cytoplasmic inclusion bodies in stained blood smears from infected fish. The causative agent, erythrocytic necrosis virus (ENV), is unculturable and a presumed iridovirus by electron microscopy. In vivo amplification of the virus in pathogen-free laboratory stocks of Pacific herring with subsequent virus concentration, purification, DNA extraction, and high-throughput sequencing were used to obtain genomic ENV sequences. Fragments with the highest sequence identity to the family Iridoviridae were used to design four sets of ENV-specific polymerase chain reaction (PCR) primers. Testing of blood and tissue samples from experimentally and wild infected Pacific herring as well as DNA extracted from other amphibian and piscine iridoviruses verified the assays were specific to ENV with a limit of detection of 0.0003 ng. Preliminary phylogenetic analyses of a 1448 bp fragment of the putative DNA polymerase gene supported inclusion of ENV in a proposed sixth genus of the family Iridoviridae that contains other erythrocytic viruses from ectothermic hosts. This study provides the first molecular evidence of ENV's inclusion within the Iridoviridae family and offers conventional PCR assays as a means of rapidly surveying the ENV-status of wild and propagated Pacific herring stocks.
Enhanced detection of infectious hematopoietic necrosis virus by pretreatment of cell monolayers with polyethylene glycol
Batts, W.N.; Winton, J.R.
To improve quantification of very low levels of infectious hematopoietic necrosis virus (IHNV) in samples of tissue, ovarian fluid, or natural water supplies, we tested the ability of polyethylene glycol (PEG) to enhance the sensitivity and speed of the plaque assay system. We compared 4, 7, and 10% solutions of PEG of molecular weight 6,000, 8,000, or 20,000 applied at selected volumes and for various durations. When cell monolayers of epithelioma papulosum cyprini (EPC), fathead minnow (FHM), chinook salmon embryo (CHSE-214), and bluegill fry (BF2) were pretreated with 7% PEG-20,000, they produced 4-17-fold increases in plaque assay titers of IHNV. The plaque assay titers of viral hemorrhagic septicemia virus, chum salmon reovirus, and chinook salmon paramyxovirus were also enhanced by exposure of CHSE-214 cells to PEG, but the titers of infectious pancreatic necrosis virus and Oncorhynchus masou virus were not substantially changed. Plaques formed by IHNV on PEG-treated EPC cells incubated at 15°C had a larger mean diameter at 6 d than those on control cells at 8 d; this suggests the assay could be shortened by use of PEG. Pretreatment of EPC cell monolayers with PEG enabled detection of IHNV in some samples that appeared negative with untreated cells. For example, when ovarian fluid samples from chinook salmon Oncorhynchus tshawytscha were inoculated onto untreated monolayers of EPC cells, IHNV was detected in only 11 of 51 samples; 17 of the samples were positive when PEG-treated EPC cells were used.PDF
Complete Genomic Characterization of Plum bark necrosis stem pitting–associated virus Infecting Sweet Cherry in China
Wang, Jiawei; Zhai, Ying; Liu, Weizhen; Zhu, Dongzi
Plum bark necrosis stem pitting–associated virus (PBNSPaV) causes the plum bark necrosis stem pitting–associated disease. We obtained the complete genome of a PBNSPaV isolate (PBNSPaV-TA) using small RNA deep sequencing followed by overlapping RT-PCR. To our knowledge, this is the first report of a completed genome of PBNSPaV identified from cherry trees. PMID:27198034
Complete Genomic Characterization of Plum bark necrosis stem pitting-associated virus Infecting Sweet Cherry in China.
Wang, Jiawei; Zhai, Ying; Liu, Weizhen; Zhu, Dongzi; Pappu, Hanu R; Liu, Qingzhong
Plum bark necrosis stem pitting-associated virus (PBNSPaV) causes the plum bark necrosis stem pitting-associated disease. We obtained the complete genome of a PBNSPaV isolate (PBNSPaV-TA) using small RNA deep sequencing followed by overlapping RT-PCR. To our knowledge, this is the first report of a completed genome of PBNSPaV identified from cherry trees. PMID:27198034
Infectious hematopoietic necrosis virus: Monophyletic origin of European isolates from North American Genogroup M
Enzmann, P.-J.; Kurath, G.; Fichtner, D.; Bergmann, S.M.
Infectious hematopoietic necrosis virus (IHNV) was first detected in Europe in 1987 in France and Italy, and later, in 1992, in Germany. The source of the virus and the route of introduction are unknown. The present study investigates the molecular epidemiology of IHNV outbreaks in Germany since its first introduction. The complete nucleotide sequences of the glycoprotein (G) and non-virion (NV) genes from 9 IHNV isolates from Germany have been determined, and this has allowed the identification of characteristic differences between these isolates. Phylogenetic analysis of partial G gene sequences (mid-G, 303 nucleotides) from North American IHNV isolates (Kurath et al. 2003) has revealed 3 major genogroups, designated U, M and L. Using this gene region with 2 different North American IHNV data sets, it was possible to group the European IHNV strains within the M genogroup, but not in any previously defined subgroup. Analysis of the full length G gene sequences indicated that an independent evolution of IHN viruses had occurred in Europe. IHN viruses in Europe seem to be of a monophyletic origin, again most closely related to North American isolates in the M genogroup. Analysis of the NV gene sequences also showed the European isolates to be monophyletic, but resolution of the 3 genogroups was poor with this gene region. As a result of comparative sequence analyses, several different genotypes have been identified circulating in Europe. ?? Inter-Research 2005.
Genetic analyses reveal unusually high diversity of infectious haematopoietic necrosis virus in rainbow trout aquaculture
Troyer, Ryan M.; LaPatra, Scott E.; Kurath, Gael
Infectious haematopoietic necrosis virus (IHNV) is the most significant virus pathogen of salmon and trout in North America. Previous studies have shown relatively low genetic diversity of IHNV within large geographical regions. In this study, the genetic heterogeneity of 84 IHNV isolates sampled from rainbow trout (Oncorhynchus mykiss) over a 20 year period at four aquaculture facilities within a 12 mile stretch of the Snake River in Idaho, USA was investigated. The virus isolates were characterized using an RNase protection assay (RPA) and nucleotide sequence analyses. Among the 84 isolates analysed, 46 RPA haplotypes were found and analyses revealed a high level of genetic heterogeneity relative to that detected in other regions. Sequence analyses revealed up to 7·6% nucleotide divergence, which is the highest level of diversity reported for IHNV to date. Phylogenetic analyses identified four distinct monophyletic clades representing four virus lineages. These lineages were distributed across facilities, and individual facilities contained multiple lineages. These results suggest that co-circulating IHNV lineages of relatively high genetic diversity are present in the IHNV populations in this rainbow trout culture study site. Three of the four lineages exhibited temporal trends consistent with rapid evolution.
Universal reverse-transcriptase real-time PCR for infectious hematopoietic necrosis virus (IHNV)
Purcell, Maureen K.; Thompson, Rachel L.; Garver, Kyle A.; Hawley, Laura M.; Batts, William N.; Sprague, Laura; Sampson, Corie; Winton, James R.
Infectious hematopoietic necrosis virus (IHNV) is an acute pathogen of salmonid fishes in North America, Europe and Asia and is reportable to the World Organization for Animal Health (OIE). Phylogenetic analysis has identified 5 major virus genogroups of IHNV worldwide, designated U, M, L, E and J; multiple subtypes also exist within those genogroups. Here, we report the development and validation of a universal IHNV reverse-transcriptase real-time PCR (RT-rPCR) assay targeting the IHNV nucleocapsid (N) gene. Properties of diagnostic sensitivity (DSe) and specificity (DSp) were defined using laboratory-challenged steelhead trout Oncorhynchus mykiss, and the new assay was compared to the OIE-accepted conventional PCR test and virus isolation in cell culture. The IHNV N gene RT-rPCR had 100% DSp and DSe and a higher estimated diagnostic odds ratio (DOR) than virus culture or conventional PCR. The RT-rPCR assay was highly repeatable within a laboratory and highly reproducible between laboratories. Field testing of the assay was conducted on a random sample of juvenile steelhead collected from a hatchery raceway experiencing an IHN epizootic. The RT-rPCR detected a greater number of positive samples than cell culture and there was 40% agreement between the 2 tests. Overall, the RT-rPCR assay was highly sensitive, specific, repeatable and reproducible and is suitable for use in a diagnostic setting.
Emergence of MD type infectious hematopoietic necrosis virus in Washington State coastal steelhead trout
Breyta, Rachel; Jones, Amelia; Stewart, Bruce; Brunson, Ray; Thomas, Joan; Kerwin, John; Bertolini, Jim; Mumford, Sonia; Patterson, Chris; Kurath, Gael
Infectious hematopoietic necrosis virus (IHNV) occurs in North America as 3 major phylogenetic groups designated U, M, and L. In coastal Washington State, IHNV has historically consisted of U genogroup viruses found predominantly in sockeye salmon Oncorhynchus nerka. M genogroup IHNV, which has host-specific virulence for rainbow and steelhead trout O. mykiss, was detected only once in coastal Washington prior to 2007, in an epidemic among juvenile steelhead trout in 1997. Beginning in 2007 and continuing through 2011, there were 8 IHNV epidemics in juvenile steelhead trout, involving 7 different fish culture facilities in 4 separate watersheds. During the same time period, IHNV was also detected in asymptomatic adult steelhead trout from 6 coastal watersheds. Genetic typing of 283 recent virus isolates from coastal Washington revealed that the great majority were in the M genogroup of IHNV and that there were 2 distinct waves of viral emergence between the years 2007 and 2011. IHNV type mG110M was dominant in coastal steelhead trout during 2007 to 2009, and type mG139M was dominant between 2010 and 2011. Phylogenetic analysis of viral isolates indicated that all coastal M genogroup viruses detected in 1997 and 2007 to 2011 were part of the MD subgroup and that several novel genetic variants related to the dominant types arose in the coastal sites. Comparison of spatial and temporal incidence of coastal MD viruses with that of the rest of the Pacific Northwest indicated that the likely source of the emergent viruses was Columbia River Basin steelhead trout.
Emergence of MD type infectious hematopoietic necrosis virus in Washington State coastal steelhead trout.
Breyta, Rachel; Jones, Amelia; Stewart, Bruce; Brunson, Ray; Thomas, Joan; Kerwin, John; Bertolini, Jim; Mumford, Sonia; Patterson, Chris; Kurath, Gael
Infectious hematopoietic necrosis virus (IHNV) occurs in North America as 3 major phylogenetic groups designated U, M, and L. In coastal Washington State, IHNV has historically consisted of U genogroup viruses found predominantly in sockeye salmon Oncorhynchus nerka. M genogroup IHNV, which has host-specific virulence for rainbow and steelhead trout O. mykiss, was detected only once in coastal Washington prior to 2007, in an epidemic among juvenile steelhead trout in 1997. Beginning in 2007 and continuing through 2011, there were 8 IHNV epidemics in juvenile steelhead trout, involving 7 different fish culture facilities in 4 separate watersheds. During the same time period, IHNV was also detected in asymptomatic adult steelhead trout from 6 coastal watersheds. Genetic typing of 283 recent virus isolates from coastal Washington revealed that the great majority were in the M genogroup of IHNV and that there were 2 distinct waves of viral emergence between the years 2007 and 2011. IHNV type mG110M was dominant in coastal steelhead trout during 2007 to 2009, and type mG139M was dominant between 2010 and 2011. Phylogenetic analysis of viral isolates indicated that all coastal M genogroup viruses detected in 1997 and 2007 to 2011 were part of the MD subgroup and that several novel genetic variants related to the dominant types arose in the coastal sites. Comparison of spatial and temporal incidence of coastal MD viruses with that of the rest of the Pacific Northwest indicated that the likely source of the emergent viruses was Columbia River Basin steelhead trout. PMID:23759556
Viral interference between infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus in Litopenaeus vannamei.
Bonnichon, Valérie; Lightner, Donald V; Bonami, Jean-Robert
White spot syndrome virus (WSSV) is highly virulent and has caused significant production losses to the shrimp culture industry over the last decade. Infectious hypodermal and hematopoietic necrosis virus (IHHNV) also infects penaeid shrimp and, while being less important than WSSV, remains a major cause of significant production losses in Litopenaeus vannamei (also called Penaeus vannamei) and L. stylirostris (also called Penaeus stylirostris). These 2 viruses and their interactions were previously investigated in L. stylirostris. We report here laboratory challenge studies carried out to determine if viral interference between IHHNV and WSSV also occurs in L. vannamei, and it was found that experimental infection with IHHNV induced a significant delay in mortality following WSSV challenge. L. vannamei infected per os with IHHNV were challenged with WSSV at 0, 10, 20, 30, 40 and 50 d post-infection. Groups of naïve shrimp infected with WSSV alone died in 3 d whereas shrimp pre-infected with IHHNV for 30, 40 or 50 d died in 5 d. Real-time PCR analysis showed that the delay correlated to the IHHNV load and that WSSV challenge induced a decrease in IHHNV load, indicating some form of competition between the 2 viruses. PMID:17140141
Differential virulence mechanisms of infectious hematopoietic necrosis virus in rainbow trout (Oncorhynchus mykiss) include host entry and virus replication kinetics
Penaranda, M.M.D.; Purcell, M.K.; Kurath, G.
Host specificity is a phenomenon exhibited by all viruses. For the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV), differential specificity of virus strains from the U and M genogroups has been established both in the field and in experimental challenges. In rainbow trout (Oncorhynchus mykiss), M IHNV strains are consistently more prevalent and more virulent than U IHNV. The basis of the differential ability of these two IHNV genogroups to cause disease in rainbow trout was investigated in live infection challenges with representative U and M IHNV strains. When IHNV was delivered by intraperitoneal injection, the mortality caused by U IHNV increased, indicating that the low virulence of U IHNV is partly due to inefficiency in entering the trout host. Analyses of in vivo replication showed that U IHNV consistently had lower prevalence and lower viral load than M IHNV during the course of infection. In analyses of the host immune response, M IHNV-infected fish consistently had higher and longer expression of innate immune-related genes such as Mx-1. This suggests that the higher virulence of M IHNV is not due to suppression of the immune response in rainbow trout. Taken together, the results support a kinetics hypothesis wherein faster replication enables M IHNV to rapidly achieve a threshold level of virus necessary to override the strong host innate immune response. ?? 2009 SGM.
First report of soybean vein necrosis disease caused by soybean vein necrosis-associated virus in Wisconsin and Iowa
Technology Transfer Automated Retrieval System (TEKTRAN)
Several viral diseases of soybean (Glycine max) have been previously identified in the north-central U.S. soybean production area, which includes Wisconsin and Iowa (Hartman et al., 1999). In September 2012, soybean plants with symptoms similar to those reported for soybean vein necrosis disease (SV...
Susceptibility of Koi and Yellow Perch to infectious hematopoietic necrosis virus by experimental exposure
Palmer, Alexander D.; Emmenegger, Eveline J.
Infectious hematopoietic necrosis virus (IHNV) is a novirhabdoviral pathogen that originated in western North America among anadromous Pacific salmonids. Severe disease epidemics in the late 1970s resulting from IHNV's invasion into farmed Rainbow Trout Oncorhynchus mykiss in North America, Asia, and Europe emphasized IHNV's ability to adapt to new hosts under varying rearing conditions. Yellow Perch Perca flavescens and Koi Carp Cyprinus carpio (hereafter, "Koi") are aquaculture-reared fish that are highly valued in sport fisheries and the ornamental fish trade, respectively, but it is unknown whether these fish species are vulnerable to IHNV infection. In this study, we exposed Yellow Perch, Koi, and steelhead (anadromous Rainbow Trout) to IHNV by intraperitoneal injection (106 PFU/fish) and by immersion (5.7×105 PFU/mL) for 7 h, and monitored fish for 28 d. The extended immersion exposure and high virus concentrations used in the challenges were to determine if the tested fish had any level of susceptibility. After experimental exposure, Yellow Perch and Koi experienced low mortality (35%). Virus was found in dead fish of all species tested and in surviving Yellow Perch by plaque assay and quantitative reverse transcription polymerase chain reaction (qPCR), with a higher prevalence in Yellow Perch than Koi. Infectious virus was also detected in Yellow Perch out to 5 d after bath challenge. These findings indicate that Yellow Perch and Koi are highly resistant to IHNV disease under the conditions tested, but Yellow Perch are susceptible to infection and may serve as possible virus carriers.
Differential susceptibility in steelhead trout populations to an emergent MD strain of infectious hematopoietic necrosis virus
Breyta, R.; Jones, Amelia; Kurath, Gael
A significant emergence of trout-adapted MD subgroup infectious hematopoietic necrosis virus (IHNV) began in the coastal region of Washington State, USA, in 2007. This emergence event lasted until 2011 and caused both asymptomatic adult fish infection and symptomatic epidemic disease and mortality in juvenile fish. Incidence of virus during this emergence demonstrated a heterogeneous distribution among rivers of the coastal region, leaving fish populations of some rivers apparently untouched while others suffered significant and recurrent infection and mortality (Breyta et. al. 2013; Dis Aquat Org 104:179-195). In this study, we examined the possible contribution of variations in susceptibility of fish populations, age-related resistance, and virus virulence to the observed landscape heterogeneity. We found that the most significant variable was host susceptibility: by controlled experimental challenge studies steelhead trout populations with no history of IHNV infection were 1 to 3 orders of magnitude more sensitive than a fish population with a long history of IHNV infection. In addition, 2 fish populations from the same river, which descended relatively recently from a common ancestral population, demonstrated 1 to 2 orders of magnitude difference in susceptibility. Fish age-related development of resistance was most evident in the more susceptible of 2 related fish populations. Finally, the strain of virus involved in the 2007 coastal Washington emergence had high virulence but was within the range of other known M group viruses tested. These results suggest that one major driver of landscape heterogeneity in the 2007 coastal Washington IHNV emergence was variation in fish population susceptibility and that this trait may have a heritable component.
Differential susceptibility in steelhead trout populations to an emergent MD strain of infectious hematopoietic necrosis virus.
Breyta, Rachel; Jones, Amelia; Kurath, Gael
A significant emergence of trout-adapted MD subgroup infectious hematopoietic necrosis virus (IHNV) began in the coastal region of Washington State, USA, in 2007. This emergence event lasted until 2011 and caused both asymptomatic adult fish infection and symptomatic epidemic disease and mortality in juvenile fish. Incidence of virus during this emergence demonstrated a heterogeneous distribution among rivers of the coastal region, leaving fish populations of some rivers apparently untouched while others suffered significant and recurrent infection and mortality (Breyta et. al. 2013; Dis Aquat Org 104:179-195). In this study, we examined the possible contribution of variations in susceptibility of fish populations, age-related resistance, and virus virulence to the observed landscape heterogeneity. We found that the most significant variable was host susceptibility: by controlled experimental challenge studies steelhead trout populations with no history of IHNV infection were 1 to 3 orders of magnitude more sensitive than a fish population with a long history of IHNV infection. In addition, 2 fish populations from the same river, which descended relatively recently from a common ancestral population, demonstrated 1 to 2 orders of magnitude difference in susceptibility. Fish age-related development of resistance was most evident in the more susceptible of 2 related fish populations. Finally, the strain of virus involved in the 2007 coastal Washington emergence had high virulence but was within the range of other known M group viruses tested. These results suggest that one major driver of landscape heterogeneity in the 2007 coastal Washington IHNV emergence was variation in fish population susceptibility and that this trait may have a heritable component. PMID:25392039
Isolation and partial characterization of a novel virus from different carp species suffering gill necrosis - ultrastructure and morphogenesis.
Granzow, H; Fichtner, D; Schütze, H; Lenk, M; Dresenkamp, B; Nieper, H; Mettenleiter, T C
Two isolates of a novel enveloped RNA virus were obtained from carp and koi carp with gill necrosis. Both isolates behaved identically and could be propagated in different cyprinid cell lines forming large syncytia. The virus was sensitive to lipid solvents and neither exhibited haemadsorption/haemagglutination nor reverse transcriptase activity. Mature virus particles displayed a spherical shape with diameter of 100-350 nm after negative staining and 100-300 nm in ultrathin sections, covered by short projections of 8-10 nm in length. Maturation of virus progeny was shown to occur by budding and envelopment of the filamentous helical nucleocapsids at the cell surface. A detailed comparison of ultrastructure and morphogenesis of the novel virus isolates with selected arena-, ortho- and paramyxoviruses as possible candidates for evaluation of taxonomic classification yielded no consistency in all phenotypic features. Thus, on the basis of ultrastructure the novel virus isolates could not be assigned unequivocally to any established virus family. PMID:23865968
PKR Activation Favors Infectious Pancreatic Necrosis Virus Replication in Infected Cells
Gamil, Amr A.A.; Xu, Cheng; Mutoloki, Stephen; Evensen, Øystein
The double-stranded RNA-activated protein kinase R (PKR) is a Type I interferon (IFN) stimulated gene that has important biological and immunological functions. In viral infections, in general, PKR inhibits or promotes viral replication, but PKR-IPNV interaction has not been previously studied. We investigated the involvement of PKR during infectious pancreatic necrosis virus (IPNV) infection using a custom-made rabbit antiserum and the PKR inhibitor C16. Reactivity of the antiserum to PKR in CHSE-214 cells was confirmed after IFNα treatment giving an increased protein level. IPNV infection alone did not give increased PKR levels by Western blot, while pre-treatment with PKR inhibitor before IPNV infection gave decreased eukaryotic initiation factor 2-alpha (eIF2α) phosphorylation. This suggests that PKR, despite not being upregulated, is involved in eIF2α phosphorylation during IPNV infection. PKR inhibitor pre-treatment resulted in decreased virus titers, extra- and intracellularly, concomitant with reduction of cells with compromised membranes in IPNV-permissive cell lines. These findings suggest that IPNV uses PKR activation to promote virus replication in infected cells. PMID:27338445
Molecular epidemiology of infectious hematopoietic necrosis virus reveals complex virus traffic and evolution within southern Idaho aquaculture
Troyer, R.M.; Kurath, G.
Infectious hematopoietic necrosis virus (IHNV) is a rhabdovirus which infects salmon and trout and may cause disease with up to 90% mortality. In the Hagerman Valley of Idaho, IHNV is endemic or epidemic among numerous fish farms and resource mitigation hatcheries. A previous study characterizing the genetic diversity among 84 IHNV isolates at 4 virus-endemic rainbow trout farms indicated that multiple lineages of relatively high diversity co-circulated at these facilities (Troyer et al. 2000 J Gen Virol. 81:2823-2832). We tested the hypothesis that high IHNV genetic diversity and co-circulating lineages are present in aquaculture facilities throughout this region. In this study, 73 virus isolates from 14 rainbow trout farms and 3 state hatcheries in the Hagerman Valley, isolated between 1978 and 1999, were genetically characterized by sequence analysis of a 303 nucleotide region of the glycoprotein gene. Phylogenetic and epidemiological analyses showed that multiple IHNV lineages co-circulate in a complex pattern throughout private trout farms and state hatcheries in the valley. IHNV maintained within the valley appears to have evolved significantly over the 22 yr study period.
Comparison of European systemic piscine and amphibian iridoviruses with epizootic haematopoietic necrosis virus and frog virus 3.
Ahne, W; Bearzotti, M; Bremont, M; Essbauer, S
Iridovirus-like agents isolated from systemic infected fish (Silurus glanis, SFIR; Ictalurus melas, CFIR I, CFIR II, CFIR III) and from frogs (Rana esculenta, REIR) in Europe, Epizootic Haematopoietic Necrosis Virus (EHNV) isolated in Australia from redfin perch (Perca fluviatilis), and Frog Virus 3 (FV 3) isolated from frogs (Rana pipiens) in the USA were investigated by electron microscopy, polypeptide composition, immunofluorescence, restriction endonuclease digestion, Southern-blot hybridization and polymerase chain reaction (PCR) amplification. All virus isolates proved to be similar in morphology and in size and reacted with EHNV polyclonal antiserum in the immunofluorescence. Whilst DNA restriction profiles of the European piscine isolates cleaved by BamH I were similar, they differed clearly from those of EHNV, REIR and FV 3. Southern-blot analysis of viral BamH I digested DNA using an EHNV DNA probe revealed cross-hybridization with DNA of the investigated iridoviruses. Using a set of primers designed for an open reading frame of the EHNV genome, PCR products of about 250 bp were obtained with the DNA of systemic piscine and amphibian iridoviruses. The data suggest that the systemic piscine and amphibian iridoviruses should be regarded as members of the the genus Ranavirus within the family Iridoviridae. PMID:9719770
Mitophagy switches cell death from apoptosis to necrosis in NSCLC cells treated with oncolytic measles virus.
Xia, Mao; Meng, Gang; Jiang, Aiqin; Chen, Aiping; Dahlhaus, Meike; Gonzalez, Patrick; Beltinger, Christian; Wei, Jiwu
Although apoptotic phenomena have been observed in malignant cells infected by measles virus vaccine strain Edmonston B (MV-Edm), the precise oncolytic mechanisms are poorly defined. In this study we found that MV-Edm induced autophagy and sequestosome 1-mediated mitophagy leading to decreased cytochrome c release, which blocked the pro-apoptotic cascade in non-small cell lung cancer cells (NSCLCs). The decrease of apoptosis by mitophagy favored viral replication. Persistent viral replication sustained by autophagy ultimately resulted in necrotic cell death due to ATP depletion. Importantly, when autophagy was impaired in NSCLCs MV-Edm-induced cell death was significantly abrogated despite of increased apoptosis. Taken together, our results define a novel oncolytic mechanism by which mitophagy switches cell death from apoptosis to more efficient necrosis in NSCLCs following MV-Edm infection. This provides a foundation for future improvement of oncolytic virotherapy or antiviral therapy. PMID:25004098
Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis.
Fong, Choong Yi; Aye, Aye Mya Min; Peyman, Mohammadreza; Nor, Norazlin Kamal; Visvaraja, Subrayan; Tajunisah, Iqbal; Ong, Lai Choo
We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease. PMID:24378951
Major histocompatibility complex loci are associated with susceptibility of Atlantic salmon to infectious hematopoietic necrosis virus
Miller, Kristina M.; Winton, James R.; Schulze, Angela D.; Purcell, Maureen K.; Ming, Tobi J.
Infectious hematopoietic necrosis virus (IHNV) is one of the most significant viral pathogens of salmonids and is a leading cause of death among cultured juvenile fish. Although several vaccine strategies have been developed, some of which are highly protective, the delivery systems are still too costly for general use by the aquaculture industry. More cost effective methods could come from the identification of genes associated with IHNV resistance for use in selective breeding. Further, identification of susceptibility genes may lead to an improved understanding of viral pathogenesis and may therefore aid in the development of preventive and therapeutic measures. Genes of the major histocompatibility complex (MHC), involved in the primary recognition of foreign pathogens in the acquired immune response, are associated with resistance to a variety of diseases in vertebrate organisms. We conducted a preliminary analysis of MHC disease association in which an aquaculture strain of Atlantic salmon was challenged with IHNV at three different doses and individual fish were genotyped at three MHC loci using denaturing gradient gel electrophoresis (PCR-DGGE), followed by sequencing of all differentiated alleles. Nine to fourteen alleles per exon-locus were resolved, and alleles potentially associated with resistance or susceptibility were identified. One allele (Sasa-B-04) from a potentially non-classical class I locus was highly associated with resistance to infectious hematopoietic necrosis (p < 0.01). This information can be used to design crosses of specific haplotypes for family analysis of disease associations.
Recovery of NV Knockout Infectious Hematopoietic Necrosis Virus Expressing Foreign Genes
Biacchesi, Stéphane; Thoulouze, Maria-Isabel; Béarzotti, Monique; Yu, Yan-Xing; Brémont, Michel
Infectious hematopoietic necrosis virus (IHNV) is a Novirhabdovirus and is the causative agent of a devastating acute, lethal disease in wild and farmed rainbow trout. The virus is enzootic throughout western North America and has spread to Asia and Europe. A full-length cDNA of the IHNV antigenome (pIHNV-Pst) was assembled from subgenomic overlapping cDNA fragments and cloned in a transcription plasmid between the T7 RNA polymerase promoter and the autocatalytic hepatitis delta virus ribozyme. Recombinant IHNV (rIHNV) was recovered from fish cells at 14°C, following infection with a recombinant vaccinia virus expressing the T7 RNA polymerase (vTF7-3) and cotransfection of pIHNV-Pst together with plasmids encoding the nucleoprotein N (pT7-N), the phosphoprotein P (pT7-P), the RNA polymerase L (pT7-L), and the nonvirion protein NV (pT7-NV). When pT7-N and pT7-NV were omitted, rIHNV was also recovered, although less efficiently. Incidental mutations introduced in pIHNV-Pst were all present in the rIHNV genome; however, a targeted mutation located in the L gene was eliminated from the recombinant genome by homologous recombination with the added pT7-L expression plasmid. To investigate the role of NV protein in virus replication, the pIHNV-Pst construct was engineered such that the entire NV open reading frame was deleted and replaced by the genes encoding green fluorescent protein or chloramphenicol acetyltransferase. The successful recovery of recombinant virus expressing foreign genes instead of the NV gene demonstrated that the NV protein was not absolutely required for viral replication in cell cultures, although its presence greatly improves virus growth. The ability to generate rIHNV from cDNA provides the basis to manipulate the genome in order to engineer new live viral vaccine strains. PMID:11070023
Genotypes and phylogeographical relationships of infectious hematopoietic necrosis virus in California, USA
Kelley, G.O.; Bendorf, C.M.; Yun, S.C.; Kurath, G.; Hedrick, R.P.
Infectious hematopoietic necrosis virus (IHNV) contains 3 major genogroups in North America with discreet geographic ranges designated as upper (U), middle (M), and lower (L). A comprehensive genotyping of 237 IHNV isolates from hatchery and wild salmonids in California revealed 25 different sequence types (a to y) all in the L genogroup; specifically, the genogroup contained 14 sequence types that were unique to individual isolates as well as 11 sequence types representing 2 or more identical isolates. The most evident trend was the phylogenetic and geographical division of the L genogroup into 2 distinct subgroups designated as LI and LII. Isolates within Subgroup LI were primarily found within waterways linked to southern Oregon and northern California coastal rivers. Isolates in Subgroup LII were concentrated within inland valley watersheds that included the Sacramento River, San Joaquin River, and their tributaries. The temporal and spatial patterns of virus occurrence suggested that infections among adult Chinook salmon in the hatchery or that spawn in the river are a major source of virus potentially infecting other migrating or resident salmonids in California. Serum neutralization results of the California isolates of IHNV corroborated a temporal trend of sequence divergence; specifically, 2 progressive shifts in which more recent virus isolates represent new serotypes. A comparison of the estimates of divergence rates for Subgroup LI (1 ?? ICT5 mutations per nucleotide site per year) indicated stasis similar to that observed in the U genogroup, while the Subgroup LII rate (1 ?? 10 3 mutations per nucleotide site per year) suggested a more active evolution similar to that of the M genogroup. ?? Inter-Research 2007.
Vaccinia Virus Induces Rapid Necrosis in Keratinocytes by a STAT3-Dependent Mechanism
He, Yong; Fisher, Robert; Chowdhury, Soma; Sultana, Ishrat; Pereira, Claudia P.; Bray, Mike; Reed, Jennifer L.
Rationale Humans with a dominant negative mutation in STAT3 are susceptible to severe skin infections, suggesting an essential role for STAT3 signaling in defense against cutaneous pathogens. Methods To focus on innate antiviral defenses in keratinocytes, we used a standard model of cutaneous infection of severe combined immunodeficient mice with the current smallpox vaccine, ACAM-2000. In parallel, early events post-infection with the smallpox vaccine ACAM-2000 were investigated in cultured keratinocytes of human and mouse origin. Results Mice treated topically with a STAT3 inhibitor (Stattic) developed larger vaccinia lesions with higher virus titers and died more rapidly than untreated controls. Cultured human and murine keratinocytes infected with ACAM-2000 underwent rapid necrosis, but when treated with Stattic or with inhibitors of RIP1 kinase or caspase-1, they survived longer, produced higher titers of virus, and showed reduced activation of type I interferon responses and inflammatory cytokines release. Treatment with inhibitors of RIP1 kinase and STAT3, but not caspase-1, also reduced the inflammatory response of keratinocytes to TLR ligands. Vaccinia growth properties in Vero cells, which are known to be defective in some antiviral responses, were unaffected by inhibition of RIP1K, caspase-1, or STAT3. Conclusions Our findings indicate that keratinocytes suppress the replication and spread of vaccinia virus by undergoing rapid programmed cell death, in a process requiring STAT3. These data offer a new framework for understanding susceptibility to skin infection in patients with STAT3 mutations. Interventions which promote prompt necroptosis/pyroptosis of infected keratinocytes may reduce risks associated with vaccination with live vaccinia virus. PMID:25419841
Continuous Exposure to Infectious Pancreatic Necrosis Virus (IPNV) During Early Life Stages of Rainbow Trout, Oncorhynchus mykiss, Walbaum
Technology Transfer Automated Retrieval System (TEKTRAN)
Rainbow trout (Oncorhynchus mykiss, Walbaum) were exposed continuously to infectious pancreatic necrosis virus (IPNV) at 0, 10, 1,000, or 10,000 pfu/L of water to estimate the effects of chronic IPNV exposure on early life stages. Fish density averaged 35 fish/L (low) or 140 fish/L (high), and wate...
Continuous exposure to infectious pancreatic necrosis virus during early life stages of rainbow trout, Oncorhynchus mykiss(Walbaum)
Technology Transfer Automated Retrieval System (TEKTRAN)
Rainbow trout (Oncorhynchus mykiss, Walbaum) were exposed continuously to infectious pancreatic necrosis virus (IPNV) at 0, 10, 1,000, or 100,000 pfu/L of water to estimate the effects of chronic IPNV exposure on early life stages. Fish density averaged 35 fish/L or 140 fish/L, with a tank flow rat...
Atomic Structure of Cucumber Necrosis Virus and the Role of the Capsid in Vector Transmission
Li, Ming; Kakani, Kishore; Katpally, Umesh; Johnson, Sharnice; Rochon, D'Ann
Cucumber Necrosis Virus (CNV) is a member of the genus Tombusvirus and has a monopartite positive-sense RNA genome packaged in a T=3 icosahedral particle. CNV is transmitted in nature via zoospores of the fungus Olpidium bornovanus. CNV undergoes a conformational change upon binding to the zoospore that is required for transmission, and specific polysaccharides on the zoospore surface have been implicated in binding. To better understand this transmission process, we have determined the atomic structure of CNV. As expected, being a member of the Tombusvirus genus, the core structure of CNV is highly similar to that of Tomato bushy stunt virus (TBSV), with major differences lying on the exposed loops. Also, as was seen with TBSV, CNV appears to have a calcium binding site between the subunits around the quasi-3-fold axes. However, unlike TBSV, there appears to be a novel zinc binding site within the β annulus formed by the N termini of the three C subunits at the icosahedral 3-fold axes. Two of the mutations causing defective transmission map immediately around this zinc binding site. The other mutations causing defective transmission and particle formation are mapped onto the CNV structure, and it is likely that a number of the mutations affect zoospore transmission by affecting conformational transitions rather than directly affecting receptor binding. PMID:24006433
Groundnut Bud Necrosis Virus Encoded NSm Associates with Membranes via Its C-Terminal Domain
Singh, Pratibha; Indi, Shantinath S.; Savithri, Handanahal S.
Groundnut Bud Necrosis Virus (GBNV) is a tripartite ambisense RNA plant virus that belongs to serogroup IV of Tospovirus genus. Non-Structural protein-m (NSm), which functions as movement protein in tospoviruses, is encoded by the M RNA. In this communication, we demonstrate that despite the absence of any putative transmembrane domain, GBNV NSm associates with membranes when expressed in E. coli as well as in N. benthamiana. Incubation of refolded NSm with liposomes ranging in size from 200–250 nm resulted in changes in the secondary and tertiary structure of NSm. A similar behaviour was observed in the presence of anionic and zwitterionic detergents. Furthermore, the morphology of the liposomes was found to be modified in the presence of NSm. Deletion of coiled coil domain resulted in the inability of in planta expressed NSm to interact with membranes. Further, when the C-terminal coiled coil domain alone was expressed, it was found to be associated with membrane. These results demonstrate that NSm associates with membranes via the C-terminal coiled coil domain and such an association may be important for movement of viral RNA from cell to cell. PMID:24919116
Binding kinetics of grouper nervous necrosis viruses with functionalized antimicrobial peptides by nanomechanical detection.
Kuan, Shu; Chi, Shau-Chi; Cheng, Yung-Jen; Chia, Ta-Jui; Huang, Long-Sun
We report the binding kinetics of fish-infected grouper nervous necrosis viruses (NNV) and selected antimicrobial peptides (AMPs) by nanomechanical detection. AMPs, the vital member in an innate immunity, are promising candidates in the fight against pathogens due to their broad range of antimicrobial activity and low toxicity. Grouper NNV primarily cause mass mortality of many marine cultured fish species, and two selected AMPs in this study were found to inhibit viruses by agglutinating its virions to form aggregates. The binding activity of NNVs with functionalized AMPs onto a sensing microcantilever yielded induced surface stresses, indicating high binding strength of molecular interaction. The binding affinity and kinetic rate constants of molecular recognition events calculated for NNV-AMP(TH1-5) compared to NNV-AMP(cSALF) were found to be 2.1-fold and 4.43-fold, respectively, indicating TH1-5 effectively bind with NNV more than cSALF. Moreover, a microscopic X-ray photoelectron spectroscopy technique was employed for further validation of pre- and post-NNV binding onto peptides-functionalized sensing surface. An increase in the spectrum and intensity of the P 2p and N 1s elements for the post-NNV binding was clearly shown to ensure the existence of phosphate groups and nitrogen-containing ring structures of specific NNV-TH1-5 interaction. Therefore, the microcantilever biosensing technique provides a potential and useful screening of AMPs for affinity to NNVs. PMID:22035974
Infectious hypodermal and hematopoietic necrosis virus from Brazil: Sequencing, comparative analysis and PCR detection.
Silva, Douglas C D; Nunes, Allan R D; Teixeira, Dárlio I A; Lima, João Paulo M S; Lanza, Daniel C F
A 3739 nucleotide fragment of Infectious hypodermal and hematopoietic necrosis virus (IHHNV) from Brazil was amplified and sequenced. This fragment contains the entire coding sequences of viral proteins, the full 3' untranslated region (3'UTR) and a partial sequence of 5' untranslated region (5'UTR). The genome organization of IHHNV revealed the three typical major coding domains: a left ORF1 of 2001 bp that codes NS1, a left ORF2 (NS2) of 1091 bp that codes NS2 and a right ORF3 of 990 bp that codes VP. Nucleotide and amino acid sequences of the three viral proteins were compared with putative amino acid sequences of viruses reported from different regions. Comparisons among genomes from different geographic locations reveal 31 nucleotide regions that are 100% similar, distributed throughout the genome. An analysis of secondary structure of UTR regions, revealed regions with high probability to form hairpins, that may be involved in mechanisms of viral replication. Additionally, a maximum likelihood analysis indicates that Brazilian IHHNV belongs to lineage III, in the infectious IHHNV group, and is clustered with IHHNV isolates from Hawaii, China, Taiwan, Vietnam and South Korea. A new nested PCR targeting conserved nucleotide regions is proposed to detect IHHNV. PMID:24867614
Research Studies on the Life Cycle of Infectious Hematopoietic Necrosis Virus.
Ristow, Sandra S.; Arnzen, Jeanene M.; Leong, JoAnn Ching
Seventeen strains of infectious hematopoietic necrosis virus (IHNV) from different geographical regions and from different fish stocks were typed by polyacrylamide gel electrophoresis, indirect fluorescence with 27 monoclonal antibodies against both the G and N proteins of the virus, and by serum neutralization with six monoclonal anti-glycoprotein antibodies. In addition, many other IHNV isolates have been examined. Studying the isolates with the antibodies has shown that a greater amount of variation exists between isolates than was first predicted by the application of the polyacrylamide technique. Isolates within electrophoretic types I-V may be further classified according to their reactions with the monoclonal antibodies in indirect fluorescence. Serum neutralization with selected anti-glycoprotein antibodies in conjunction with fluorescence analysis confirms one of the original findings of Hsu et al. (1986) that two different species in a single facility can be infected with the same isolate. Variation among isolates as measured by reactivity with the monoclonal library appears to be greater within the G protein than within the N protein sequence. 9 refs., 7 figs., 6 tabs.
Improved self-inactivating retroviral vectors derived from spleen necrosis virus.
Olson, P; Nelson, S; Dornburg, R
Self-inactivating (SIN) retroviral vectors contain a deletion spanning most of the right long terminal repeat's (LTR's) U3 region. Reverse transcription copies this deletion to both LTRs. As a result, there is no transcription from the 5' LTR, preventing further replication. Many previously developed SIN vectors, however, had reduced titers or were genetically unstable. Earlier, we reported that certain SIN vectors derived from spleen necrosis virus (SNV) experienced reconstitution of the U3-deleted LTR at high frequencies. This reconstitution occurred on the DNA level and appeared to be dependent on defined vector sequences. To study this phenomenon in more detail, we developed an almost completely U3-free retroviral vector. The promoter and enhancer of the left LTR were replaced with those of the cytomegalovirus immediate-early genes. This promoter swap did not impair the level of transcription or alter its start site. Our data indicate that SNV contains a strong initiator which resembles that of human immunodeficiency virus. We show that the vectors replicate with efficiencies similar to those of vectors possessing two wild-type LTRs. U3-deleted vectors carrying the hygromycin B phosphotransferase gene did not observably undergo LTR reconstitution, even when replicated in helper cells containing SNV-LTR sequences. However, vectors carrying the neomycin resistance gene did undergo LTR reconstitution with the use of homologous helper cell LTR sequences as template. This supports our earlier finding that sequences within the neomycin resistance gene can trigger recombination. Images PMID:7933088
Fish DNA vaccine against infectious hematopoietic necrosis virus: efficacy of various routes of immunization
Corbeil, Serge; Kurath, Gael; LaPatra, Scott E.
The DNA vaccine, pIHNVw-G, contains the gene for the glycoprotein (G) of the rhabdovirus infectious hematopoietic necrosis virus (IHNV), a major pathogen of salmon and trout. The relative efficacy of various routes of immunisation with pIHNVw-G was evaluated using 1.8 g rainbow trout fry vaccinated via intramuscular injection, scarification of the skin, intraperitoneal injection, intrabuccal administration, cutaneous particle bombardment using a gene gun, or immersion in water containing DNA vaccine-coated beads. Twenty-seven days after vaccination neutralising antibody titres were determined, and 2 days later groups of vaccinated and control unvaccinated fish were subjected to an IHNV immersion challenge. Results of the virus challenge showed that the intramuscular injection and the gene gun immunisation induced protective immunity in fry, while intraperitoneal injection provided partial protection. Neutralising antibodies were not detected in sera of vaccinated fish regardless of the route of immunisation used, suggesting that cell mediated immunity may be at least partially responsible for the observed protection.
GHSC70 Is Involved in the Cellular Entry of Nervous Necrosis Virus
Chang, Jui-Shin
ABSTRACT Nervous necrosis virus (NNV) is a devastating pathogen of cultured marine fish and has affected more than 40 fish species. NNV belongs to the betanodaviruses of Nodaviridae and is a nonenveloped icosahedral particle with 2 single-stranded positive-sense RNAs. To date, knowledge regarding NNV entry into the host cell remains limited, and no NNV-specific receptor protein has been published. Using grouper fin cell line GF-1 and purified NNV capsid protein in a virus overlay protein binding assay (VOPBA), grouper heat shock cognate protein 70 (GHSC70) and grouper voltage-dependent anion selective channel protein 2 (GVDAC2) were investigated as NNV receptor protein candidates. We cloned and sequenced the genes for GHSC70 and GVDAC2 and expressed them in Escherichia coli for antiserum preparation. Knockdown of the expression of GHSC70 and GVDAC2 genes with specific short interfering RNAs (siRNAs) significantly downregulated viral RNA expression in NNV-infected GF-1 cells. By performing an immunoprecipitation assay, we confirmed that GHSC70 interacted with NNV capsid protein, while VDAC2 did not. Immunofluorescence staining and flow cytometry analysis revealed the presence of the GHSC70 protein on the cell surface. After a blocking assay, we detected the NNV RNA2 levels after 1 h of adsorption to GF-1 cells; the level was significantly lower in the cells pretreated with the GHSC70 antiserum than in nontreated cells. Therefore, we suggest that GHSC70 participates in the NNV entry of GF-1 cells, likely functioning as an NNV receptor or coreceptor protein. IMPORTANCE Fish nodavirus has caused mass mortality of more than 40 fish species worldwide and resulted in huge economic losses in the past 20 years. Among the four genotypes of fish nodaviruses, the red-spotted grouper nervous necrosis virus (RGNNV) genotype exhibits the widest host range. In our previous study, we developed monoclonal antibodies with high neutralizing efficiency against grouper NNV in GF-1 cells
Targeted gene transfer to lymphocytes using murine leukaemia virus vectors pseudotyped with spleen necrosis virus envelope proteins.
Engelstädter, M; Buchholz, C J; Bobkova, M; Steidl, S; Merget-Millitzer, H; Willemsen, R A; Stitz, J; Cichutek, K
In contrast to murine leukaemia virus (MLV)-derived vector systems, vector particles derived from the avian spleen necrosis virus (SNV) have been successfully targeted to subsets of human cells by envelope modification with antibody fragments (scFv). However, an in vivo application of the SNV vector system in gene transfer protocols is hampered by its lack of resistance against human complement. To overcome this limitation we established pseudotyping of MLV vector particles produced in human packaging cell lines with the SNV envelope (Env) protein. Three variants of SNV Env proteins differing in the length of their cytoplasmic domains were all efficiently incorporated into MLV core particles. These pseudotype particles infected the SNV permissive cell line D17 at titers of up to 10(5) IU/ml. A stable packaging cell line (MS4) of human origin released MLV(SNV) pseudotype vectors that were resistant against human complement inactivation. To redirect their tropism to human T cells, MS4 cells were transfected with the expression gene encoding the scFv 7A5 in fusion with the transmembrane domain (TM) of the SNV Env protein, previously shown to retarget SNV vector particles to human lymphocytes. MLV(SNV-7A5)-vector particles released from these cells were selectively infectious for human T cell lines. The data provide a proof of principle for targeting MLV-derived vectors to subpopulations of human cells through pseudotyping with SNV targeting envelopes. PMID:11509952
Genetic diversity and epidemiology of infectious hematopoietic necrosis virus in Alaska
Emmenegger, E.G; Meyers, T.R.; Burton, T.O.; Kurath, G.
Forty-two infectious hematopoietic necrosis virus (IHNV) isolates from Alaska were analyzed using the ribonuclease protection assay (RPA) and nucleotide sequencing. RPA analyses, utilizing 4 probes, N5, N3 (N gene), GF (G gene), and NV (NV gene), determined that the haplotypes of all 3 genes demonstrated a consistent spatial pattern. Virus isolates belonging to the most common haplotype groups were distributed throughout Alaska, whereas isolates in small haplotype groups were obtained from only 1 site (hatchery, lake, etc.). The temporal pattern of the GF haplotypes suggested a 'genetic acclimation' of the G gene, possibly due to positive selection on the glycoprotein. A pairwise comparison of the sequence data determined that the maximum nucleotide diversity of the isolates was 2.75% (10 mismatches) for the NV gene, and 1.99% (6 mismatches) for a 301 base pair region of the G gene, indicating that the genetic diversity of IHNV within Alaska is notably lower than in the more southern portions of the IHNV North American range. Phylogenetic analysis of representative Alaskan sequences and sequences of 12 previously characterized IHNV strains from Washington, Oregon, Idaho, California (USA) and British Columbia (Canada) distinguished the isolates into clusters that correlated with geographic origin and indicated that the Alaskan and British Columbia isolates may have a common viral ancestral lineage. Comparisons of multiple isolates from the same site provided epidemiological insights into viral transmission patterns and indicated that viral evolution, viral introduction, and genetic stasis were the mechanisms involved with IHN virus population dynamics in Alaska. The examples of genetic stasis and the overall low sequence heterogeneity of the Alaskan isolates suggested that they are evolutionarily constrained. This study establishes a baseline of genetic fingerprint patterns and sequence groups representing the genetic diversity of Alaskan IHNV isolates. This
Mapping the neutralizing epitopes on the glycoprotein of infectious haematopoietic necrosis virus, a fish rhabdovirus
Huang, C.; Chien, M.S.; Landolt, M.L.; Batts, W.; Winton, J.
Twelve neutralizing monoclonal antibodies (MAbs) against the fish rhabdovirus, infectious haematopoietic necrosis virus (IHNV), were used to select 20 MAb escape mutants. The nucleotide sequence of the entire glycoprotein (G) gene was determined for six mutants representing differing cross-neutralization patterns and each had a single nucleotide change leading to a single amino acid substitution within one of three regions of the protein. These data were used to design nested PCR primers to amplify portions of the G gene of the 14 remaining mutants. When the PCR products from these mutants were sequenced, they also had single nucleotide substitutions coding for amino acid substitutions at the same, or nearby, locations. Of the 20 mutants for which all or part of the glycoprotein gene was sequenced, two MAbs selected mutants with substitutions at amino acids 230-231 (antigenic site I) and the remaining MAbs selected mutants with substitutions at amino acids 272-276 (antigenic site II). Two MAbs that selected mutants mapping to amino acids 272-276, selected other mutants that mapped to amino acids 78-81, raising the possibility that this portion of the N terminus of the protein was part of a discontinuous epitope defining antigenic site II. CLUSTAL alignment of the glycoproteins of rabies virus, vesicular stomatitis virus and IHNV revealed similarities in the location of the neutralizing epitopes and a high degree of conservation among cysteine residues, indicating that the glycoproteins of three different genera of animal rhabdoviruses may share a similar three-dimensional structure in spite of extensive sequence divergence.
Genetic characterization of infectious hematopoietic necrosis virus of coastal salmonid stocks in Washington State
Emmenegger, E.J.; Kurath, G.
Infectious hematopoietic necrosis virus (IHNV) is a pathogen that infects many Pacific salmonid stocks from the watersheds of North America. Previous studies have thoroughly characterized the genetic diversity of IHNV isolates from Alaska and the Hagerman Valley in Idaho. To enhance understanding of the evolution and viral transmission patterns of IHNV within the Pacific Northwest geographic range, we analyzed the G gene of IHNV isolates from the coastal watersheds of Washington State by ribonuclease protection assay (RPA) and nucleotide sequencing. The RPA analysis of 23 isolates indicated that the Skagit basin IHNV isolates were relatively homogeneous as a result of the dominance of one G gene haplotype (S). Sequence analysis of 303 bases in the middle of the G gene (midG region) of 61 isolates confirmed the high frequency of a Skagit River basin sequence and identified another sequence commonly found in isolates from the Lake Washington basin. Overall, both the RPA and sequence analysis showed that the Washington coastal IHNV isolates are genetically homogeneous and have little genetic diversity. This is similar to the genetic diversity pattern of IHNV from Alaska and contrasts sharply with the high genetic diversity demonstrated for IHNV isolates from fish farms along the Snake River in Idaho. The high degree of sequence and haplotype similarity between the Washington coastal IHNV isolates and those from Alaska and British Columbia suggests that they have a common viral ancestor. Phylogenetic analyses of the isolates we studied and those from different regions throughout the virus's geographic range confirms a conserved pattern of evolution of the virus in salmonid stocks north of the Columbia River, which forms Washington's southern border.
Encapsidation of Host RNAs by Cucumber Necrosis Virus Coat Protein during both Agroinfiltration and Infection
Ghoshal, Kankana; Theilmann, Jane; Reade, Ron; Maghodia, Ajay
ABSTRACT Next-generation sequence analysis of virus-like particles (VLPs) produced during agroinfiltration of cucumber necrosis virus (CNV) coat protein (CP) and of authentic CNV virions was conducted to assess if host RNAs can be encapsidated by CNV CP. VLPs containing host RNAs were found to be produced during agroinfiltration, accumulating to approximately 1/60 the level that CNV virions accumulated during infection. VLPs contained a variety of host RNA species, including the major rRNAs as well as cytoplasmic, chloroplast, and mitochondrial mRNAs. The most predominant host RNA species encapsidated in VLPs were chloroplast encoded, consistent with the efficient targeting of CNV CP to chloroplasts during agroinfiltration. Interestingly, droplet digital PCR analysis showed that the CNV CP mRNA expressed during agroinfiltration was the most efficiently encapsidated mRNA, suggesting that the CNV CP open reading frame may contain a high-affinity site or sites for CP binding and thus contribute to the specificity of CNV RNA encapsidation. Approximately 0.09% to 0.7% of the RNA derived from authentic CNV virions contained host RNA, with chloroplast RNA again being the most prominent species. This is consistent with our previous finding that a small proportion of CNV CP enters chloroplasts during the infection process and highlights the possibility that chloroplast targeting is a significant aspect of CNV infection. Remarkably, 6 to 8 of the top 10 most efficiently encapsidated nucleus-encoded RNAs in CNV virions correspond to retrotransposon or retrotransposon-like RNA sequences. Thus, CNV could potentially serve as a vehicle for horizontal transmission of retrotransposons to new hosts and thereby significantly influence genome evolution. IMPORTANCE Viruses predominantly encapsidate their own virus-related RNA species due to the possession of specific sequences and/or structures on viral RNA which serve as high-affinity binding sites for the coat protein. In this study
Genetic and serological typing of European infectious haematopoietic necrosis virus (IHNV) isolates
Johansson, T.; Einer-Jensen, K.; Batts, W.; Ahrens, P.; Bjorkblom, C.; Kurath, G.; Bjorklund, H.; Lorenzen, N.
Infectious haematopoietic necrosis virus (IHNV) causes the lethal disease infectious haematopoietic necrosis (IHN) in juvenile salmon and trout. The nucleocapsid (N) protein gene and partial glycoprotein (G) gene (nucleotides 457 to 1061) of the European isolates IT-217A, FR-32/87, DE-DF 13/98 11621, DE-DF 4/99-8/99, AU-9695338 and RU-FR1 were sequenced and compared with IHNV isolates from the North American genogroups U, M and L. In phylogenetic studies the N gene of the Italian, French, German and Austrian isolates clustered in the M genogroup, though in a different subgroup than the isolates from the USA. Analyses of the partial G gene of these European isolates clustered them in the M genogroup close to the root while the Russian isolate clustered in the U genogroup. The European isolates together with US-WRAC and US-Col-80 were also tested in an enzyme-linked immunosorbent assay (ELISA) using monoclonal antibodies (MAbs) against the N protein. MAbs 136-1 and 136-3 reacted equally at all concentrations with the isolates tested, indicating that these antibodies identify a common epitope. MAb 34D3 separated the M and L genogroup isolates from the U genogroup isolate. MAb 1DW14D divided the European isolates into 2 groups. MAb 1DW14D reacted more strongly with DE-DF 13/98 11621 and RU-FR1 than with IT-217A, FR- 32/87, DE-DF 4/99-8/99 and AU-9695338. In the phylogenetic studies, the Italian, French, German and Austrian isolates clustered in the M genogroup, whereas in the serological studies using MAbs, the European M genogroup isolates could not be placed in the same specific group. These results indicate that genotypic and serotypic classification do not correlate. ?? 2009 Inter-Research.
Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice.
Gilles, P N; Fey, G; Chisari, F V
It is well known that several inflammatory cytokines can modulate hepatocellular gene expression in a complex physiological process known as the hepatic acute-phase response. Since hepatitis B virus (HBV) characteristically induces a vigorous lymphomononuclear inflammatory response in the liver during acute and chronic hepatitis, it is possible that hepatocellular HBV gene expression may also be modulated by one or more of the cytokines produced by these cells. Using bacterial lipopolysaccharide (LPS) as a surrogate inducer of inflammatory cytokines in vivo, we have tested this hypothesis in a transgenic mouse model system. In experiments with two independent transgenic mouse lineages that express the HBV envelope region under the control of either HBV or cellular promoters, we observed a 50 to 80% reduction in the hepatic steady-state content of a 2.1-kb HBV mRNA following administration of a single intraperitoneal dose of LPS. The regulatory influence of several inflammatory cytokines known to be induced by LPS was also examined in this system. The negative regulatory effect of LPS was consistently reproduced by the administration of a single nontoxic dose of tumor necrosis factor alpha, and it was occasionally observed following the administration of high doses of alpha interferon and interleukin-6, while no effect was detectable in response to high-dose interleukin-1 alpha or to gamma interferon. These observations suggest that tumor necrosis factor alpha and perhaps other cytokines may activate a heretofore unsuspected intracellular pathway that negatively regulates HBV gene expression. The intracellular mechanism(s) responsible for this effect and its pathophysiologic relevance remain to be elucidated. Images PMID:1583737
Factors predicting kidney damage in Puumala virus infected patients in Southern Denmark.
Skarphedinsson, S; Thiesson, H C; Shakar, S A; Tepel, M
In Europe, infections with Puumala hantavirus cause nephropathia epidemica. Presently the risk factors predicting severe kidney damage after Puumala virus infection are not well known. The objective of the study was to investigate environmental and individual factors predicting severe kidney damage caused by serologically established Puumala infections. In a nationwide cohort study we investigated all serologically established Puumala infections in Southern Denmark from 1996 to 2012. A total of 184 patients had serologically verified Puumala virus infection. In patients with Puumala virus infections the decrease of platelet counts preceded acute kidney failure. Multivariable logistic regression demonstrated that recent activities in the forest, platelet counts, and flu-like symptoms predicted estimated glomerular filtration rates less than 30 mL/min/1.73 m(²), but not age, gender, fever, nor abdominal pain. Severe kidney damage in Puumala infections in Southern Denmark is associated with the risk of recent activities in the forest. PMID:26205664
Kidney lesions associated with mortality in chickens inoculated with waterfowl influenza viruses
Slemons, R.D.; Locke, L.N.; Sheerar, Martha G.; Duncan, R.M.; Hinshaw, Virginia S.; Easterday, B.C.
Seventy-six type A influenza viruses recovered from waterfowl in Wisconsin, California, South Dakota, Florida, Texas, Alabama, and Nebraska were tested for virulence in chickens. The challenge to chickens was intravenous inoculation of first-, second-, or third-egg-passage virus. Each of the virus strains was tested separately in three or four chickens. Eighteen of the 76 viruses caused the death of one or more chickens following inoculation. Postmortem lesions were similar in all dead birds. In decreasing order of frequency, gross lesions included: swollen kidneys evident as accentuated lobular patterns, urates in the pericardial sac, and urates on the surface of the liver. Microscopic lesions present in kidneys were consistent with visceral gout. Mortality was associated with inoculations having higher concentrations of infectious virus. These results indicate that the influenza A viruses circulating in duck populations may include strains potentially pathogenic for chickens.
Seed Transmission of Soybean vein necrosis virus: The First Tospovirus Implicated in Seed Transmission
Groves, Carol; German, Thomas; Dasgupta, Ranjit; Mueller, Daren; Smith, Damon L.
Soybean vein necrosis virus (SVNV; genus Tospovirus; Family Bunyaviridae) is a negative-sense single-stranded RNA virus that has been detected across the United States and in Ontario, Canada. In 2013, a seed lot of a commercial soybean variety (Glycine max) with a high percentage of discolored, deformed and undersized seed was obtained. A random sample of this seed was planted in a growth room under standard conditions. Germination was greater than 90% and the resulting seedlings looked normal. Four composite samples of six plants each were tested by reverse transcription polymerase chain reaction (RT-PCR) using published primers complimentary to the S genomic segment of SVNV. Two composite leaflet samples retrieved from seedlings yielded amplicons with a size and sequence predictive of SVNV. Additional testing of twelve arbitrarily selected individual plants resulted in the identification of two SVNV positive plants. Experiments were repeated by growing seedlings from the same seed lot in an isolated room inside a thrips-proof cage to further eliminate any external source of infection. Also, increased care was taken to reduce any possible PCR contamination. Three positive plants out of forty-eight were found using these measures. Published and newly designed primers for the L and M RNAs of SVNV were also used to test the extracted RNA and strengthen the diagnosis of viral infection. In experiments, by three scientists, in two different labs all three genomic RNAs of SVNV were amplified in these plant materials. RNA-seq analysis was also conducted using RNA extracted from a composite seedling sample found to be SVNV-positive and a symptomatic sample collected from the field. This analysis revealed both sense and anti-sense reads from all three gene segments in both samples. We have shown that SVNV can be transmitted in seed to seedlings from an infected seed lot at a rate of 6%. To our knowledge this is the first report of seed-transmission of a Tospovirus. PMID
Evidence for and characterization of nervous necrosis virus infection in Pacific cod (Gadus macrocephalus).
Mao, Ming-Guang; Wen, Shi-Hui; Perálvarez-Marín, Alex; Li, Hua; Jiang, Jie-Lan; Jiang, Zhi-Qiang; Li, Xing; Sun, Hang; Lü, Hui-Qian
A mortality rate higher than 90% was observed in a larva-rearing facility for Pacific cod, Gadus macrocephalus, in China. Larvae showing clinical signs of infection were collected. Initial suspicion of nervous necrosis virus (NNV) infection was confirmed by sequencing, absolute quantification real-time PCR (A-qPCR), and electron microscopy. The nucleotide sequence of RNA2 was 1,375 bases long (GenBank no. KM576685), coding for a single ORF corresponding to the capsid protein from residues 21 to 1034. Phylogenetic analysis of the capsid protein sequence showed that PCNNV belongs to the barfin flounder NNV (BFNVV) genotype. An amino acid sequence alignment revealed 39 differences between the cold- and warm-resistant viral groups, suggesting that PCNNV evolved under temperature selection. The 3-D structure of the predicted capsid protein was modeled to identify potential epitopes, and the gene was expressed in Escherichia coli, yielding a protein with a molecular mass of 55 kDa. During PCNNV outbreaks, the viral copy number was found to reach 10(7) per ng of total RNA, which could be considered the lethal copy number of NNV in cod. The gonads, eggs, fertilized eggs and asymptomatic cod fry were all positive for PCNNV, indicating viral vertical transmission as the main source of the viral load. The amount of virus in the apparent healthy fry or survivors seemed to decrease gradually with development. These results might lead to efficient diagnostic methods to help farmers select NNV-free broodfish for cod breeding. PMID:26115691
Immunogenicity of synthetic peptides representing neutralizing epitopes on the glycoprotein of infectious hematopoietic necrosis virus
Emmenegger, E.; Landolt, M.; LaPatra, S.; Winton, J.
Three peptides, P76, P226, and P268 representing 3 putative antigen~c determinants on the glycoprotein of infectious hematopoietic necrosis virus (IHNV), were synthesized and injected into rainbow trout Oncorhynchus mykiss to assess their immunogen~city. Antisera extracted from the immunized trout were analyzed uslng an enzyme linked imrnunosorbent assay (ELISA) for the presence of antibodies that could bind to the peptides or to intact virions of IHNV. The antisera were also tested for neutralizing activity against IHNV by a complement-mediated neutralization assay. In general, recognition of the peptides and IHNV was low and only a few antibody binding patterns were demonstrated. Antisera from fish injected with P76 constructs recognized the homologous peptide more than the heterologous peptides, whereas antisera from fish inoculated with either P226 or P268 constructs recognized P76 equally, or better, than the homologous peptide; however, there was a high degree of individual variation within each treatment group. Neutralization actlvlty was demonstrated by serum from a single flsh lnlected with one of the pept~des (P268) and from 7 of 10 positive control f~sh Infected with an attenuated strain of IHNV Possible explanations for the dichotomous immune responses are discussed. These results indicate we need to improve our overall understanding of the
Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection
Konnai, Satoru . E-mail: email@example.com; Usui, Tatsufumi; Ikeda, Manabu; Kohara, Junko; Hirata, Toh-ichi; Okada, Kosuke; Ohashi, Kazuhiko; Onuma, Misao
Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-{alpha} and an imbalance of TNF receptors in sheep experimentally infected with bovine leukemia virus (BLV). In order to investigate the different TNF-{alpha}-induced responses, in this study we examined the TNF-{alpha}-induced proliferative response and the expression levels of two distinct TNF receptors on peripheral blood mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The proliferative response of PBMC isolated from those cattle with PL in the presence of recombinant bovine TNF-{alpha} (rTNF-{alpha}) was significantly higher than those from AL cattle and uninfected cattle and the cells from PL cattle expressed significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels. Most cells expressing TNF-RII in PL cattle were CD5{sup +} or sIgM{sup +} cells and these cells showed resistance to TNF-{alpha}-induced apoptosis. Additionally, there were significant positive correlations between the changes in provirus load and TNF-RII mRNA levels, and TNF-{alpha}-induced proliferation and TNF-RII mRNA levels. These data suggest that imbalance in the expression of TNF receptors could at least in part contribute to the progression of lymphocytosis in BLV infection.
Hepatic expression of tumour necrosis factor-alpha in chronic hepatitis B virus infection.
Hussain, M J; Lau, J Y; Williams, R; Vergani, D
AIM--To determine the hepatic expression of tumour necrosis factor-alpha (TNF alpha) in patients with chronic hepatitis B virus (HBV) infection. METHODS--Frozen liver biopsy sections from 19 patients with chronic HBV infection were studied, 12 of whom were HBeAg positive and 10 serum HBV DNA positive. Hepatic expression of TNF alpha was determined using immunohistochemistry. RESULTS--Only infiltrating mononuclear cells showed immunoreactive staining for TNF alpha (median 2, range 0-3; n = 19) which appeared as diffuse positive staining material in the cytoplasm. Patients with active liver disease, assessed histologically and biochemically, had a higher level of expression, both in the number of TNF alpha positive cells and the proportion of TNF alpha positive infiltrating mononuclear cells. There was no correlation between the expression of TNF alpha and serological parameters of viral infection (HBeAg and HBV DNA status and HBV DNA concentrations). CONCLUSION--Hepatic expression of TNF alpha is increased in chronic HBV infection and is related to the activity of liver disease and not to the level of HBV replication. Images PMID:7876386
African Swine Fever Virus Infection Induces Tumor Necrosis Factor Alpha Production: Implications in Pathogenesis
Gómez del Moral, M.; Ortuño, E.; Fernández-Zapatero, P.; Alonso, F.; Alonso, C.; Ezquerra, A.; Domínguez, J.
We have analyzed the production of tumor necrosis factor alpha (TNF-α) induced by in vitro infection with African swine fever (ASF) virus (ASFV) and the systemic and local release of this inflammatory cytokine upon in vivo infection. An early increase in TNF-α mRNA expression was detected in ASFV-infected alveolar macrophages, and high levels of TNF-α protein were detected by ELISA in culture supernatants from these cells. When animals were experimentally infected with a virulent isolate (E-75), enhanced TNF-α expression in mainly affected organs correlated with viral protein expression. Finally, elevated levels of TNF-α were detected in serum, corresponding to the onset of clinical signs. TNF-α has been reported to be critically involved in the pathogenesis of major clinical events in ASF, such as intravascular coagulation, tissue injury, apoptosis, and shock. In the present study, TNF-α containing supernatants from ASFV-infected cultures induced apoptosis in uninfected lymphocytes; this effect was partially abrogated by preincubation with an anti-TNF-α specific antibody. These results suggest a relevant role for TNF-α in the pathogenesis of ASF. PMID:9971800
Dialysis buffer with different ionic strength affects the antigenicity of cultured nervous necrosis virus (NNV) suspensions.
Gye, Hyun Jung; Nishizawa, Toyohiko
Nervous necrosis virus (NNV) belongs to the genus Betanodavirus (Nodaviridae). It is highly pathogenic to various marine fishes. Here, we investigated the antigenicity changes of cultured NNV suspensions during 14days of dialyses using a dialysis tube at 1.4×10(4) molecular weight cut off (MWCO) in three different buffers (Dulbecco's phosphate buffered saline (D-PBS), 15mM Tris-HCl (pH 8.0), and deionized water (DIW)). Total NNV antigen titers of cultured NNV suspension varied depending on different dialysis buffers. For example, total NNV antigen titer during D-PBS dialysis was increased once but then decreased. During Tris-HCl dialysis, it was relatively stable. During dialysis in DIW, total NNV antigen titer was increased gradually. These antigenicity changes in NNV suspension might be due to changes in the aggregation state of NNV particles and/or coat proteins (CPs). ELISA values of NNV suspension changed due to changing aggregates state of NNV antigens. NNV particles in suspension were aggregated at a certain level. These aggregates were progressive after D-PBS dialysis, but regressive after Tris-HCl dialysis. The purified NNV particles self-aggregated after dialysis in D-PBS or in Tris-HCl containing 600mM NaCl, but not after dialysis in Tris-HCl or DIW. Quantitative analysis is merited to determine NNV antigens in the highly purified NNV particles suspended in buffer at low salt condition. PMID:27381060
Susceptibility of Chinese Perch Brain (CPB) Cell and Mandarin Fish to Red-Spotted Grouper Nervous Necrosis Virus (RGNNV) Infection.
Tu, Jiagang; Chen, Wenjie; Fu, Xiaozhe; Lin, Qiang; Chang, Ouqin; Zhao, Lijuan; Lan, Jiangfeng; Li, Ningqiu; Lin, Li
Nervous necrosis virus (NNV) is the causative agent of viral encephalopathy and retinopathy (VER), a neurological disease responsible for high mortality of fish species worldwide. Taking advantage of our established Chinese perch brain (CPB) cell line derived from brain tissues of Mandarin fish (Siniperca chuatsi), the susceptibility of CPB cell to Red-Spotted Grouper nervous necrosis virus (RGNNV) was evaluated. The results showed that RGNNV replicated well in CPB cells, resulting in cellular apoptosis. Moreover, the susceptibility of Mandarin fish to RGNNV was also evaluated. Abnormal swimming was observed in RGNNV-infected Mandarin fish. In addition, the cellular vacuolation and viral particles were also observed in brain tissues of RGNNV-infected Mandarin fish by Hematoxylin-eosin staining or electronic microscopy. The established RGNNV susceptible brain cell line from freshwater fish will pave a new way for the study of the pathogenicity and replication of NNV in the future. PMID:27213348
Susceptibility of Chinese Perch Brain (CPB) Cell and Mandarin Fish to Red-Spotted Grouper Nervous Necrosis Virus (RGNNV) Infection
Tu, Jiagang; Chen, Wenjie; Fu, Xiaozhe; Lin, Qiang; Chang, Ouqin; Zhao, Lijuan; Lan, Jiangfeng; Li, Ningqiu; Lin, Li
Nervous necrosis virus (NNV) is the causative agent of viral encephalopathy and retinopathy (VER), a neurological disease responsible for high mortality of fish species worldwide. Taking advantage of our established Chinese perch brain (CPB) cell line derived from brain tissues of Mandarin fish (Siniperca chuatsi), the susceptibility of CPB cell to Red-Spotted Grouper nervous necrosis virus (RGNNV) was evaluated. The results showed that RGNNV replicated well in CPB cells, resulting in cellular apoptosis. Moreover, the susceptibility of Mandarin fish to RGNNV was also evaluated. Abnormal swimming was observed in RGNNV-infected Mandarin fish. In addition, the cellular vacuolation and viral particles were also observed in brain tissues of RGNNV-infected Mandarin fish by Hematoxylin-eosin staining or electronic microscopy. The established RGNNV susceptible brain cell line from freshwater fish will pave a new way for the study of the pathogenicity and replication of NNV in the future. PMID:27213348
Appearance and quantification of infectious hematopoietic necrosis virus in female sockeye salmon (Oncorhynchus nerka) during their spawning migration
Mulcahy, D.; Jenes, C.K.; Pascho, R.J.
The incidence and amount of infectious hematopoietic necrosis (IHN) virus was determined in 10 organs and body fluids from each of 100 female sockeye salmon(Oncorhynchus nerka) before, during, and after their spawning migration into freshwater. Virus was found in high concentrations only in fish sampled during and after spawning. Infection rates increased from nil to 100 percent within 2 weeks. In spawning fish, incidences of IHN virus were high in all organs and fluids except brain and serum, and the highest concentrations were in the pyloric caeca and lower gut. Immediately before spawning, IHN virus was found most frequently in the gills, less frequently in the pyloric caeca and spleen, and rarely in other organs.
Nervous Necrosis Virus Replicates Following the Embryo Development and Dual Infection with Iridovirus at Juvenile Stage in Grouper
Hsu, Hao-Hsuan; Chen, Peng-Peng; Lee, Szu-Hsien; Chen, Young-Mao; Tsai, Tieh-Jung; Wang, Chien-Kai; Ku, Hsiao-Tung; Lee, Gwo-Bin; Chen, Tzong-Yueh
Infection of virus (such as nodavirus and iridovirus) and bacteria (such as Vibrio anguillarum) in farmed grouper has been widely reported and caused large economic losses to Taiwanese fish aquaculture industry since 1979. The multiplex assay was used to detect dual viral infection and showed that only nervous necrosis virus (NNV) can be detected till the end of experiments (100% mortality) once it appeared. In addition, iridovirus can be detected in a certain period of rearing. The results of real-time PCR and in situ PCR indicated that NNV, in fact, was not on the surface of the eggs but present in the embryo, which can continue to replicate during the embryo development. The virus may be vertically transmitted by packing into eggs during egg development (formation) or delivering into eggs by sperm during fertilization. The ozone treatment of eggs may fail to remove the virus, so a new strategy to prevent NNV is needed. PMID:22563447
The kinetics and protection of the antiviral state induced by recombinant iIFN1a in rainbow trout against infectious hematopoietic necrosis virus.
Cao, Yongsheng; Xu, Liming; LaPatra, Scott E; Zhao, Jingzhuang; Liu, Miao; Liu, Hongbai; Lu, Tongyan; Zhang, Qiya
The iIFN1a (intracellular IFN-a1), that is one of the IFN-a1 variants, was shown to be functional intracellularly and act as a novel defense against an infectious hematopoietic necrosis virus (IHNV). To determine its antiviral properties, a recombinant iIFN1a was generated in Escherichia coli. Its antiviral activity against IHNV was 1.69×10(7)U/mg in CHSE-214 cells. Additionally, iIFN1a was capable of inducing comparable levels of IRF-1, IRF-2, IFN-I, IFN-γ and Mx transcription in head kidney, spleen and liver tissues at an early time point (6h), that was followed by a rapid decline 24h after induction. The recombinant protein also elicited protection against IHNV in vivo. At 6 and 24h after induction there was 100% protection against the virus, however, at 48 and 72h the protection decreased to 57 and 40%, respectively. The in vivo protection kinetics correlated with the kinetics of gene expression. The results of this study provide details of the antiviral state that was induced by iIFN1a in vivo for the first time. Additionally, this information will facilitate the development of this recombinant protein as a potential anti-viral treatment and/or adjuvant. PMID:27348633
Estimation of Parameters Influencing Waterborne Transmission of Infectious Hematopoietic Necrosis Virus (IHNV) in Atlantic Salmon (Salmo salar)
Garver, Kyle A; Mahony, Amelia A. M.; Stucchi, Dario; Richard, Jon; Van Woensel, Cecile; Foreman, Mike
Understanding how pathogenic organisms spread in the environment is crucial for the management of disease, yet knowledge of propagule dispersal and transmission in aquatic environments is limited. We conducted empirical studies using the aquatic virus, infectious hematopoietic necrosis virus (IHNV), to quantify infectious dose, shedding capacity, and virus destruction rates in order to better understand the transmission of IHN virus among Atlantic salmon marine net-pen aquaculture. Transmission of virus and subsequent mortality in Atlantic salmon post-smolts was initiated with as low as 10 plaque forming units (pfu) ml−1. Virus shedding from IHNV infected Atlantic salmon was detected before the onset of visible signs of disease with peak shed rates averaging 3.2×107 pfu fish−1 hour−1 one to two days prior to mortality. Once shed into the marine environment, the abundance of free IHNV is modulated by sunlight (UV A and B) and the growth of natural biota present in the seawater. Virus decayed very slowly in sterilized seawater while rates as high as k = 4.37 d−1 were observed in natural seawater. Decay rates were further accelerated when exposed to sunlight with virus infectivity reduced by six orders of magnitude within 3 hours of full sunlight exposure. Coupling the IHNV transmission parameter estimates determined here with physical water circulation models, will increase the understanding of IHNV dispersal and provide accurate geospatial predictions of risk for IHNV transmission from marine salmon sites. PMID:24340016
Local Production of Tumor Necrosis Factor Encoded by Recombinant Vaccinia Virus is Effective in Controlling Viral Replication in vivo
NASA Astrophysics Data System (ADS)
Sambhi, Sharan K.; Kohonen-Corish, Maija R. J.; Ramshaw, Ian A.
Tumor necrosis factor (TNF) has pleiotropic effects on a wide variety of cell types. In vitro studies have demonstrated that TNF has antiviral properties and is induced in response to viral infections. However, a role for TNF in the antiviral immune response of the host has yet to be demonstrated. Here we describe the construction of and studies using a recombinant vaccinia virus that encodes the gene for murine TNF-α. By comparing the replication of and immune responses elicited by the TNF-encoding virus to a similarly constructed control virus, we hoped to observe immunobiological effects of TNF in the host. The in vivo experiments with this recombinant virus demonstrate that the localized production of TNF-α during a viral infection leads to the rapid and efficient clearance of the virus in normal mice and attenuates the otherwise lethal pathogenicity of the virus in immunodeficient animals. This attenuation occurs early in the infection (by postinfection hour 24) and is not due to the enhancement of cellular or antibody responses by the vaccinia virus-encoded TNF. This evidence suggests that attenuation of the recombinant virus is due to a direct antiviral effect of TNF on cells at the site of infection. Therefore, these results support the suggestion that TNF produced by immune cells may be an important effector mechanism of viral clearance in vivo.
Resistance and Protective Immunity in Redfish Lake Sockeye Salmon Exposed to M Type Infectious Hematopoietic Necrosis Virus (IHNV)
Kurath, Gael; Garver, Kyle; Purcell, Maureen K.; LaPatra, Scott E.
Differential virulence of infectious hematopoietic necrosis virus (IHNV) isolates from the U and M phylogenetic subgroups is clearly evident in the Redfish Lake (RFL) strain of sockeye salmon Oncorhynchus nerka. In these fish, experimental immersion challenges with U isolates cause extremely high mortality and M isolates cause low or no mortality. When survivors of M virus immersion challenges were exposed to a secondary challenge with virulent U type virus they experienced high mortality, indicating that the primary M challenge did not elicit protective immunity. Delivery of a moderate dose (2 × 104 plaque-forming units [PFU]/fish) of virus by intraperitoneal injection challenge did not overcome RFL sockeye salmon resistance to M type IHNV. Injection challenge with a high dose (5 × 106 PFU/fish) of M type virus caused 10% mortality, and in this case survivors did develop protective immunity against a secondary U type virus challenge. Thus, although it is possible for M type IHNV to elicit cross-protective immunity in this disease model, it does not develop after immersion challenge despite entry, transient replication of M virus to low levels, stimulation of innate immune genes, and development of neutralizing antibodies in some fish.
Genetic variation underlying resistance to infectious hematopoietic necrosis virus in a steelhead trout (Oncorhynchus mykiss) population
Brieuc, Marine S. O.; Purcell, Maureen K.; Palmer, Alexander D.; Naish, Kerry A.
Understanding the mechanisms of host resistance to pathogens will allow insights into the response of wild populations to the emergence of new pathogens. Infectious hematopoietic necrosis virus (IHNV) is endemic to the Pacific Northwest and infectious to Pacific salmon and trout (Oncorhynchus spp.). Emergence of the M genogroup of IHNV in steelhead trout O. mykiss in the coastal streams of Washington State, between 2007 and 2011, was geographically heterogeneous. Differences in host resistance due to genetic change were hypothesized to be a factor influencing the IHNV emergence patterns. For example, juvenile steelhead trout losses at the Quinault National Fish Hatchery (QNFH) were much lower than those at a nearby facility that cultures a stock originally derived from the same source population. Using a classical quantitative genetic approach, we determined the potential for the QNFH steelhead trout population to respond to selection caused by the pathogen, by estimating the heritability for 2 traits indicative of IHNV resistance, mortality (h2 = 0.377 (0.226 - 0.550)) and days to death (h2 = 0.093 (0.018 - 0.203)). These results confirm that there is a genetic basis for resistance and that this population has the potential to adapt to IHNV. Additionally, genetic correlation between days to death and fish length suggests a correlated response in these traits to selection. Reduction of genetic variation, as well as the presence or absence of resistant alleles, could affect the ability of populations to adapt to the pathogen. Identification of the genetic basis for IHNV resistance could allow the assessment of the susceptibility of other steelhead populations.
Pathophysiology of infectious hematopoietic necrosis virus disease in rainbow trout (Salmo gairdneri): early changes in blood and aspects of the immune Response after Injection of IHN Virus
Amend, Donald F.; Smith, Lynnwood
Juvenile rainbow trout (Salmo gairdneri) were injected with infectious hematopoietic necrosis (IHN) virus and various hematological and blood chemical changes were monitored over 9 days. The packed cell volume, hemoglobin, red blood cell count, and plasma bicarbonate were significantly depressed by day 4. Plasma chloride, calcium, phosphorus, total protein, and blood cell types did not change during the 9 days. Furthermore, plasma LDH isozyme was significantly increased by the fourth day, and fish infected with infectious pancreatic necrosis virus, Vibrio anguillarum, Aeromonas salmonicida, and redmouth bacterium did not show specific LDH isozyme alterations. Acid-base alterations occurred at 10 C but not at 18 C. The acid-base imbalance and elevation of the LDH isozyme were consistently associated with the early development of the disease.The immune response after injection of IHN virus was determined and protection from disease was tested by passive immunization. Actively immunized fish developed IHN-neutralizing antibodies within 54 days after injection of virus, and the antibodies were protective when juvenile fish were passively immunized and experimentally challenged with IHN virus.
Protective immunity against nervous necrosis virus in convict grouper Epinephelus septemfasciatus following vaccination with virus-like particles produced in yeast Saccharomyces cerevisiae.
Wi, Ga Ram; Hwang, Jee Youn; Kwon, Mun-Gyeong; Kim, Hyoung Jin; Kang, Hyun Ah; Kim, Hong-Jin
Infection with nervous necrosis virus (NNV) causes viral nervous necrosis, which inflicts serious economic losses in marine fish cultivation. Virus-like particles (VLPs) are protein complexes consisting of recombinant virus capsid proteins, whose shapes are similar to native virions. VLPs are considered a novel vaccine platform because they are not infectious and have the ability to induce neutralizing antibodies efficiently. However, there have been few studies of protective immune responses employing virus challenge following immunization with NNV VLPs, and this is important for evaluating the utility of the vaccine. In the present study, we produced red-spotted grouper (Epinephelus akaara) NNV (RGNNV) VLPs in Saccharomyces cerevisiae and investigated protective immune responses in convict grouper (Epinephelus septemfasciatus) following intraperitoneal injection and oral immunization with the RGNNV VLPs. The parenterally administered VLPs elicited neutralizing antibody with high efficacy, and provided the fish with full protection against RGNNV challenge: 100% of the immunized fish survived compared with only 37% of the control fish receiving phosphate-buffered saline. RGNNV VLPs administered orally provoked neutralizing antibody systemically and conferred protective immunity against virus challenge: however only 57% of the fish survived. Our results demonstrate that RGNNV VLP produced in yeast has great potential as vaccine in fish. PMID:25759291
Protection of rainbow trout against infectious hematopoietic necrosis virus four days after specific or semi-specific DNA vaccination
LaPatra, S.E.; Corbeil, S.; Jones, G.R.; Shewmaker, W.D.; Lorenzen, N.; Anderson, E.D.; Kurath, G.
A DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was shown to provide significant protection as soon as 4 d after intramuscular vaccination in 2 g rainbow trout (Oncorhynchus mykiss) held at 15??C. Nearly complete protection was also observed at later time points (7, 14, and 28 d) using a standardized waterborne challenge model. In a test of the specificity of this early protection, immunization of rainbow trout with a DNA vaccine against another fish rhabdovirus, viral hemorrhagic septicemia virus, provided a significant level of cross-protection against IHNV challenge for a transient period of time, whereas a rabies virus DNA vaccine was not protective. This indication of distinct early and late protective mechanisms was not dependent on DNA vaccine doses from 0.1 to 2.5 ??g. ?? 2001 Elsevier Science Ltd.
Induction of necrosis via mitochondrial targeting of Melon necrotic spot virus replication protein p29 by its second transmembrane domain
Mochizuki, Tomofumi; Hirai, Katsuyuki; Kanda, Ayami; Ohnishi, Jun; Ohki, Takehiro; Tsuda, Shinya
The virulence factor of Melon necrotic spot virus (MNSV), a virus that induces systemic necrotic spot disease on melon plants, was investigated. When the replication protein p29 was expressed in N. benthamiana using a Cucumber mosaic virus vector, necrotic spots appeared on the leaf tissue. Transmission electron microscopy revealed abnormal mitochondrial aggregation in these tissues. Fractionation of tissues expressing p29 and confocal imaging using GFP-tagged p29 revealed that p29 associated with the mitochondrial membrane as an integral membrane protein. Expression analysis of p29 deletion fragments and prediction of hydrophobic transmembrane domains (TMDs) in p29 showed that deletion of the second putative TMD from p29 led to deficiencies in both the mitochondrial localization and virulence of p29. Taken together, these results indicated that MNSV p29 interacts with the mitochondrial membrane and that p29 may be a virulence factor causing the observed necrosis.
Protection of rainbow trout against infectious hematopoietic necrosis virus four days after specific or semi-specific DNA vaccination.
LaPatra, S E; Corbeil, S; Jones, G R; Shewmaker, W D; Lorenzen, N; Anderson, E D; Kurath, G
A DNA vaccine against a fish rhabdovirus, infectious hematopoietic necrosis virus (IHNV), was shown to provide significant protection as soon as 4 d after intramuscular vaccination in 2 g rainbow trout (Oncorhynchus mykiss) held at 15 degrees C. Nearly complete protection was also observed at later time points (7, 14, and 28 d) using a standardized waterborne challenge model. In a test of the specificity of this early protection, immunization of rainbow trout with a DNA vaccine against another fish rhabdovirus, viral hemorrhagic septicemia virus, provided a significant level of cross-protection against IHNV challenge for a transient period of time, whereas a rabies virus DNA vaccine was not protective. This indication of distinct early and late protective mechanisms was not dependent on DNA vaccine doses from 0.1 to 2.5 microg. PMID:11427277
Herpes Simplex Virus 1 (HSV-1) and HSV-2 Mediate Species-Specific Modulations of Programmed Necrosis through the Viral Ribonucleotide Reductase Large Subunit R1
Yu, Xiaoliang; Li, Yun; Chen, Qin; Su, Chenhe; Zhang, Zili; Yang, Chengkui; Hu, Zhilin; Hou, Jue; Zhou, Jinying; Gong, Ling; Jiang, Xuejun
ABSTRACT Receptor-interacting protein kinase 3 (RIP3) and its substrate mixed-lineage kinase domain-like protein (MLKL) are core regulators of programmed necrosis. The elimination of pathogen-infected cells by programmed necrosis acts as an important host defense mechanism. Here, we report that human herpes simplex virus 1 (HSV-1) and HSV-2 had opposite impacts on programmed necrosis in human cells versus their impacts in mouse cells. Similar to HSV-1, HSV-2 infection triggered programmed necrosis in mouse cells. However, neither HSV-1 nor HSV-2 infection was able to induce programmed necrosis in human cells. Moreover, HSV-1 or HSV-2 infection in human cells blocked tumor necrosis factor (TNF)-induced necrosis by preventing the induction of an RIP1/RIP3 necrosome. The HSV ribonucleotide reductase large subunit R1 was sufficient to suppress TNF-induced necrosis, and its RIP homotypic interaction motif (RHIM) domain was required to disrupt the RIP1/RIP3 complex in human cells. Therefore, this study provides evidence that HSV has likely evolved strategies to evade the host defense mechanism of programmed necrosis in human cells. IMPORTANCE This study demonstrated that infection with HSV-1 and HSV-2 blocked TNF-induced necrosis in human cells while these viruses directly activated programmed necrosis in mouse cells. Expression of HSV R1 suppressed TNF-induced necrosis of human cells. The RHIM domain of R1 was essential for its association with human RIP3 and RIP1, leading to disruption of the RIP1/RIP3 complex. This study provides new insights into the species-specific modulation of programmed necrosis by HSV. PMID:26559832
Studies on uptake and intracellular processing of infectious pancreatic necrosis virus by Atlantic cod scavenger endothelial cells.
Martin-Armas, M; Sommer, A-I; Smedsrød, B
Previous work in our group has identified the scavenger endothelial cells (SECs) of heart endocardium in cod, Gadus morhua L., as the major site for elimination of both physiological and foreign macromolecular waste from the circulation. The present study was undertaken to establish the role of cod SECs in the clearance of virus. We focused on infectious pancreatic necrosis virus (IPNV) as it is a well-known virus with a broad host range, and causes significant economic losses in the salmon industry. Our results showed that cod SEC cultures infected by the IPNV produce high titres of new virus. Ligand-receptor inhibition experiments suggested that the virus did not enter the cells through any of the major endocytosis receptors of cod SECs. Yet, the infection lowered the capacity of the cells to endocytose ligands via the scavenger receptor. Inhibitors of receptor recycling and vesicle acidification did not affect virus infectivity. The finding that SEC cultures prepared from 25% of the cod produced high titres of IPNV without being infected in the laboratory, suggests that SECs of cod may serve as reservoirs for IPNV in persistently infected cod. PMID:17958614
Biochemical and antigenic properties of the first isolates of infectious hematopoietic necrosis virus from salmonid fish in Europe
Arkush, K.D.; Bovo, G.; deKinkelin, P.; Winton, J.R.; Wingfield, W.H.; Hedrick, R.P.
The first isolates of infectious hematopoietic necrosis virus (IHNV) recovered from rainbow trout Oncorhynchus mykiss (formerly Salmo gairdneri) in France and Italy were compared to six representative strains from North America by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of virion polypeptides and neutralization by monoclonal antibodies (MAbs). All three IHNV isolates from Europe had similar polypeptide profiles when compared by SDS-PAGE. An analysis of the antigenic relatedness of the European isolates to representative strains from North America showed that they were clearly different from viruses obtained from salmonids in California. The RB/B5 MAb, which was developed against virus isolated from adult steelhead (anadromous rainbow trout) reared in central Oregon, neutralized all isolates examined. The 193–110/B4 MAb, developed against IHNV isolated from infected yearling rainbow trout in southern Idaho, neutralized all isolates tested except those from California. The SRCV/A4 MAb, developed against Sacramento River chinook virus (SRCV) isolated from adult spring chinook salmon O. tshawytscha in central California, was the least reactive, and strong neutralization was observed only with the SRCV strain of IHNV from California. However, partial reactivity of the virus isolates from France with the SRCV/A4 MAb distinguished them from the virus recovered from salmonids in Italy.
Insights into Alternanthera mosaic virus TGB3 functions: Interactions with Nicotiana benthamiana PsbO correlate with chloroplast vesiculation and veinal necrosis caused by TGB3 overexpression
Technology Transfer Automated Retrieval System (TEKTRAN)
Alternanthera mosaic virus (AltMV) triple gene block 3 (TGB3) protein is involved in viral movement. AltMV TGB3 subcellular localization was previously shown to be distinct from that of Potato virus X (PVX) TGB3, and a chloroplast binding domain identified; veinal necrosis and chloroplast vesiculati...
Atlantic salmon, Salmo salar L. are broadly susceptible to isolates representing the North American genogroups of infectious hematopoietic necrosis virus
Kurath, Gael; Winton, James R.; Dale, Ole Bendik; Purcell, Maureen K.; Falk, Knut; Busch, Robert D.
Beginning in 1992, three epidemic waves of infectious hematopoietic necrosis, often with high mortality, occurred in farmed Atlantic salmon Salmo salar L. on the west coast of North America. We compared the virulence of eleven strains of infectious hematopoietic necrosis virus (IHNV), representing the U, M and L genogroups, in experimental challenges of juvenile Atlantic salmon in freshwater. All strains caused mortality and there was wide variation within genogroups: cumulative mortality for five U-group strains ranged from 20 to 100%, four M-group strains ranged 30-63% and two L-group strains varied from 41 to 81%. Thus, unlike Pacific salmonids, there was no apparent correlation of virulence in a particular host species with virus genogroup. The mortality patterns indicated two different phenotypes in terms of kinetics of disease progression and final per cent mortality, with nine strains having moderate virulence and two strains (from the U and L genogroups) having high virulence. These phenotypes were investigated by histopathology and immunohistochemistry to describe the variation in the course of IHNV disease in Atlantic salmon. The results from this study demonstrate that IHNV may become a major threat to farmed Atlantic salmon in other regions of the world where the virus has been, or may be, introduced.
Molecular characterization of the virulent infectious hematopoietic necrosis virus (IHNV) strain 220-90
Background Infectious hematopoietic necrosis virus (IHNV) is the type species of the genus Novirhabdovirus, within the family Rhabdoviridae, infecting several species of wild and hatchery reared salmonids. Similar to other rhabdoviruses, IHNV has a linear single-stranded, negative-sense RNA genome of approximately 11,000 nucleotides. The IHNV genome encodes six genes; the nucleocapsid, phosphoprotein, matrix protein, glycoprotein, non-virion protein and polymerase protein genes, respectively. This study describes molecular characterization of the virulent IHNV strain 220-90, belonging to the M genogroup, and its phylogenetic relationships with available sequences of IHNV isolates worldwide. Results The complete genomic sequence of IHNV strain 220-90 was determined from the DNA of six overlapping clones obtained by RT-PCR amplification of genomic RNA. The complete genome sequence of 220-90 comprises 11,133 nucleotides (GenBank GQ413939) with the gene order of 3'-N-P-M-G-NV-L-5'. These genes are separated by conserved gene junctions, with di-nucleotide gene spacers. An additional uracil nucleotide was found at the end of the 5'-trailer region, which was not reported before in other IHNV strains. The first 15 of the 16 nucleotides at the 3'- and 5'-termini of the genome are complementary, and the first 4 nucleotides at 3'-ends of the IHNV are identical to other novirhadoviruses. Sequence homology and phylogenetic analysis of the glycoprotein genes show that 220-90 strain is 97% identical to most of the IHNV strains. Comparison of the virulent 220-90 genomic sequences with less virulent WRAC isolate shows more than 300 nucleotides changes in the genome, which doesn't allow one to speculate putative residues involved in the virulence of IHNV. Conclusion We have molecularly characterized one of the well studied IHNV isolates, 220-90 of genogroup M, which is virulent for rainbow trout, and compared phylogenetic relationship with North American and other strains
Species differences in kidney necrosis and DNA damage, distribution and glutathione-dependent metabolism of 1,2-dibromo-3-chloropropane (DBCP).
Søderlund, E J; Låg, M; Holme, J A; Brunborg, G; Omichinski, J G; Dahl, J E; Nelson, S D; Dybing, E
Species differences and mechanisms of 1,2-dibromo-3-chloropropane (DBCP) nephrotoxicity were investigated by studying DBCP renal necrosis and DNA damage, distribution and glutathione-dependent metabolism in rats, mice, hamsters and guinea pigs. Extensive renal tubular necrosis was observed in rats 48 hr after a single intraperitoneal administration (21-170 mumol/kg) of DBCP. Significantly less necrosis was found in mice and guinea pigs, whereas no renal damage was evident (less than 680 mumol/kg) in hamsters. The activation of DBCP to DNA damaging intermediates in vivo, as measured by alkaline elution of DNA isolated from kidney nuclei 60 min. after intraperitoneal injection of DBCP, was compared in all four species. Distinct DNA damage was detected in rats, mice and hamsters as early as 10 min. after administration of DBCP and within 30 min. in guinea pigs. Rats and guinea pigs showed similar sensitivity towards DBCP-induced DNA damage (extensive DNA damage greater than 21 mumol/kg DBCP), whereas in mice and hamsters a 10-50 times higher DBCP dose was needed to cause a similar degree of DNA damage. Renal DBCP concentrations at various time-points (20 min., 1, 3 and 8 hr) after intraperitoneal administration (85 mumol/kg) revealed that the initial (20 min.) DBCP concentration was substantially higher in rats and guinea pigs compared to the other two species. Furthermore, kidney elimination of DBCP occurred at a significantly lower rate in rats than in mice, hamsters and guinea pigs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2371234
Virulence correlates with fitness in vivo for two M group genotypes of Infectious hematopoietic necrosis virus (IHNV).
Wargo, Andrew R.; Garver, Kyle A.; Kurath, Gael
The nature of the association between viral fitness and virulence remains elusive in vertebrate virus systems, partly due to a lack of in vivo experiments using statistically sufficient numbers of replicate hosts. We examined the relationship between virulence and fitness in Infectious hematopoietic necrosis virus (IHNV), in vivo, in intact living rainbow trout. Trout were infected with a high or low virulence genotype of M genogroup IHNV, or a mixture of the two genotypes, so as to calculate relative fitness and the effect of a competition environment on fitness. Fitness was measured as total viral load in the host at time of peak viral density, quantified by genotype-specific quantitative RT-PCR (qRT-PCR). The more virulent IHNV genotype reached higher densities in both single and mixed infections. There was no effect of competition on the performance of either genotype. Our results suggest a positive link between IHNV genotype fitness and virulence.
Antiviral activity of casein and αs2 casein hydrolysates against the infectious haematopoietic necrosis virus, a rhabdovirus from salmonid fish.
Rodríguez Saint-Jean, S; De las Heras, A; Carrillo, W; Recio, I; Ortiz-Delgado, J B; Ramos, M; Gomez-Ruiz, J A; Sarasquete, C; Pérez-Prieto, S I
Salmonid fish viruses, such as infectious haematopoietic necrosis virus (IHNV), are responsible for serious losses in the rainbow trout and salmon-farming industries, and they have been the subject of intense research in the field of aquaculture. Thus, the aim of this work is to study the antiviral effect of milk-derived proteins as bovine caseins or casein-derived peptides at different stages during the course of IHNV infection. The results indicate that the 3-h fraction of casein and α(S2) -casein hydrolysates reduced the yield of infectious IHNV in a dose-dependent manner and impaired the production of IHNV-specific antigens. Hydrolysates of total casein and α(S2) -casein target the initial and later stages of viral infection, as demonstrated by the reduction in the infective titre observed throughout multiple stages and cycles. In vivo, more than 50% protection was observed in the casein-treated fish, and the kidney sections exhibited none of the histopathological characteristics of IHNV infection. The active fractions from casein were identified, as well as one of the individual IHNV-inhibiting peptides. Further studies will be required to determine which other peptides possess this activity. These findings provide a basis for future investigations on the efficacy of these compounds in treating other viral diseases in farmed fish and to elucidate the underlying molecular mechanisms of action. However, the present results provide convincing evidence in support of a role for several milk casein fractions as suitable candidates to prevent and treat some fish viral infections. PMID:23167612
Influenza virus vaccination and kidney graft rejection: causality or coincidence.
Fischer, Anne Sophie Lind; Møller, Bjarne Kuno; Krag, Søren; Jespersen, Bente
Influenza can cause significant morbidity and mortality in renal transplant recipients especially with a high rate of lower respiratory disease. Annual influenza vaccination is therefore recommended to renal transplant recipients. We report the first three cases of acute kidney injury in renal transplant recipients following influenza vaccination that all led to graft loss. They all had different native diseases and were all vaccinated in the same season of 2009-10. The time span from vaccination to decline of kidney function is shorter than the time to diagnosis since the three patients only had blood tests every 3 months or when symptoms became severe. These reports do not justify a change of current recommendations regarding influenza vaccination in renal transplant recipients, but they support the continued attention and registration of vaccinations to monitor side effects. PMID:26034595
Influenza virus vaccination and kidney graft rejection: causality or coincidence
Fischer, Anne Sophie Lind; Møller, Bjarne Kuno; Krag, Søren; Jespersen, Bente
Influenza can cause significant morbidity and mortality in renal transplant recipients especially with a high rate of lower respiratory disease. Annual influenza vaccination is therefore recommended to renal transplant recipients. We report the first three cases of acute kidney injury in renal transplant recipients following influenza vaccination that all led to graft loss. They all had different native diseases and were all vaccinated in the same season of 2009–10. The time span from vaccination to decline of kidney function is shorter than the time to diagnosis since the three patients only had blood tests every 3 months or when symptoms became severe. These reports do not justify a change of current recommendations regarding influenza vaccination in renal transplant recipients, but they support the continued attention and registration of vaccinations to monitor side effects. PMID:26034595
Lettuce chlorosis virus P23 Suppresses RNA Silencing and Induces Local Necrosis with Increased Severity at Raised Temperatures.
Kubota, Kenji; Ng, James C K
RNA silencing functions as an antivirus defense strategy in plants, one that plant viruses counter by producing viral suppressors of RNA silencing (VSRs). VSRs have been identified in three members of the genus Crinivirus but they do not all share identical suppression mechanisms. Here, we used Agrobacterium co-infiltration assays to investigate the suppressor activity of proteins encoded by Lettuce chlorosis virus (LCV). Of 7 LCV proteins (1b, P23, HSP70 homolog, P60, CP, CPm, and P27) tested for the suppression of silencing of green fluorescent protein (GFP) expression in wild-type Nicotiana benthamiana plants, only P23 suppressed the onset of local silencing. Small-interfering (si)RNA accumulation was reduced in leaves co-infiltrated with P23, suggesting that P23 inhibited the accumulation or enhanced the degradation of siRNA. P23 also inhibited the cell-to-cell and systemic movement of RNA silencing in GFP-expressing transgenic N. benthamiana plants. Expression of P23 via agroinfiltration of N. benthamiana leaves induced local necrosis that increased in severity at elevated temperatures, a novelty given that a direct temperature effect on necrosis severity has not been reported for the other crinivirus VSRs. These results further affirm the sophistication of crinivirus VSRs in mediating the evasion of host's antiviral defenses and in symptom modulation. PMID:26828232
Canarypox Virus-Induced Maturation of Dendritic Cells Is Mediated by Apoptotic Cell Death and Tumor Necrosis Factor Alpha Secretion
Ignatius, Ralf; Marovich, Mary; Mehlhop, Erin; Villamide, Loreley; Mahnke, Karsten; Cox, William I.; Isdell, Frank; Frankel, Sarah S.; Mascola, John R.; Steinman, Ralph M.; Pope, Melissa
Recombinant avipox viruses are being widely evaluated as vaccines. To address how these viruses, which replicate poorly in mammalian cells, might be immunogenic, we studied how canarypox virus (ALVAC) interacts with primate antigen-presenting dendritic cells (DCs). When human and rhesus macaque monocyte-derived DCs were exposed to recombinant ALVAC, immature DCs were most susceptible to infection. However, many of the infected cells underwent apoptotic cell death, and dying infected cells were engulfed by uninfected DCs. Furthermore, a subset of DCs matured in the ALVAC-exposed DC cultures. DC maturation coincided with tumor necrosis factor alpha (TNF-α) secretion and was significantly blocked in the presence of anti-TNF-α antibodies. Interestingly, inhibition of apoptosis with a caspase 3 inhibitor also reduced some of the maturation induced by exposure to ALVAC. This indicates that both TNF-α and the presence of primarily apoptotic cells contributed to DC maturation. Therefore, infection of immature primate DCs with ALVAC results in apoptotic death of infected cells, which can be internalized by noninfected DCs driving DC maturation in the presence of the TNF-α secreted concomitantly by exposed cells. This suggests an important mechanism that may influence the immunogenicity of avipox virus vectors. PMID:11070033
Detection and Quantification of Infectious Hypodermal and Hematopoietic Necrosis Virus and White Spot Virus in Shrimp Using Real-Time Quantitative PCR and SYBR Green Chemistry
Dhar, Arun K.; Roux, Michelle M.; Klimpel, Kurt R.
A rapid and highly sensitive real-time PCR detection and quantification method for infectious hypodermal and hematopoietic necrosis virus (IHHNV), a single-stranded DNA virus, and white spot virus (WSV), a double-stranded DNA (dsDNA) virus infecting penaeid shrimp (Penaeus sp.), was developed using the GeneAmp 5700 sequence detection system coupled with SYBR Green chemistry. The PCR mixture contains a fluorescence dye, SYBR Green, which upon binding to dsDNA exhibits fluorescence enhancement. The enhancement of fluorescence was proportional to the initial concentration of the template DNA. A linear relationship was observed between the amount of input plasmid DNA and cycle threshold (CT) values over a range of 1 to 105 copies of the viral genome. To control the variation in sampling and processing among samples, the shrimp β-actin gene was amplified in parallel with the viral DNA. The CT values of IHHNV- and WSV-infected samples were used to determine absolute viral copy numbers from the standard CT curves of these viruses. For each virus and its β-actin control, the specificity of amplification was monitored by using the dissociation curve of the amplified product. Using genomic DNA as a template, SYBR Green PCR was found to be 100- to 2000-fold more sensitive than conventional PCR, depending on the virus, for the samples tested. The results demonstrate that SYBR Green PCR can be used as a rapid and highly sensitive detection and quantification method for shrimp viruses and that it is amenable to high-throughout assay. PMID:11474000
Quantitative expression profiling of immune response genes in rainbow trout following infectious haematopoietic necrosis virus (IHNV) infection or DNA vaccination
Purcell, Maureen K.; Kurath, Gael; Garver, Kyle A.; Herwig, Russell P.; Winton, James R.
Infectious haematopoietic necrosis virus (IHNV) is a well-studied virus of salmonid fishes. A highly efficacious DNA vaccine has been developed against this virus and studies have demonstrated that this vaccine induces both an early and transient non-specific anti-viral phase as well as long-term specific protection. The mechanisms of the early anti-viral phase are not known, but previous studies noted changes in Mx gene expression, suggesting a role for type I interferon. This study used quantitative real-time reverse transcriptase PCR methodology to compare expression changes over time of a number of cytokine or cytokine-related genes in the spleen of rainbow trout following injection with poly I:C, live IHNV, the IHNV DNA vaccine or a control plasmid encoding the non-antigenic luciferase gene. The target genes included Mx-1, viral haemorrhagic septicaemia virus induced gene 8 (Vig-8), TNF-α1, TNF-α2, IL-1β1, IL-8, TGF-β1 and Hsp70. Poly I:C stimulation induced several genes but the strongest and significant response was observed in the Mx-1 and Vig-8 genes. The live IHN virus induced a significant response in all genes examined except TGF-β1. The control plasmid construct and the IHNV DNA vaccine marginally induced a number of genes, but the main difference between these two groups was a statistically significant induction of the Mx-1 and Vig-8 genes by the IHNV vaccine only. The gene expression profiles elicited by the live virus and the IHNV DNA vaccine differed in a number of aspects but this study confirms the clear role for a type I interferon-like response in early anti-viral defence.
Genetic Signature of Rapid IHHNV (Infectious Hypodermal and Hematopoietic Necrosis Virus) Expansion in Wild Penaeus Shrimp Populations
Robles-Sikisaka, Refugio; Bohonak, Andrew J.; McClenaghan, Leroy R.; Dhar, Arun K.
Infectious hypodermal and hematopoietic necrosis virus (IHHNV) is a widely distributed single-stranded DNA parvovirus that has been responsible for major losses in wild and farmed penaeid shrimp populations on the northwestern Pacific coast of Mexico since the early 1990's. IHHNV has been considered a slow-evolving, stable virus because shrimp populations in this region have recovered to pre-epizootic levels, and limited nucleotide variation has been found in a small number of IHHNV isolates studied from this region. To gain insight into IHHNV evolutionary and population dynamics, we analyzed IHHNV capsid protein gene sequences from 89 Penaeus shrimp, along with 14 previously published sequences. Using Bayesian coalescent approaches, we calculated a mean rate of nucleotide substitution for IHHNV that was unexpectedly high (1.39×10−4 substitutions/site/year) and comparable to that reported for RNA viruses. We found more genetic diversity than previously reported for IHHNV isolates and highly significant subdivision among the viral populations in Mexican waters. Past changes in effective number of infections that we infer from Bayesian skyline plots closely correspond to IHHNV epizootiological historical records. Given the high evolutionary rate and the observed regional isolation of IHHNV in shrimp populations in the Gulf of California, we suggest regular monitoring of wild and farmed shrimp and restriction of shrimp movement as preventative measures for future viral outbreaks. PMID:20668694
Concentration of infectious hematopoietic necrosis virus from water samples by tangential flow filtration and polyethylene glycol precipitation
Batts, W.N.; Winton, J.R.
Infectious hematopoietic necrosis virus (IHNV) was concentrated from water samples by polyethylene glycol (PEG) precipitation, tangential flow filtration (TFF), and by a combination of TFF followed by PEG precipitation of the retentate. Used alone, PEG increased virus titers more than 200-fold, and the efficiency of recovery was as great as 100%. Used alone, TFF concentrated IHNV more than 20-fold, and average recovery was 70%. When the two techniques were combined, 10-L water samples were reduced to about 300 mL by TFF and the virus was precipitated with PEG into a 1 to 2 g pellet; total recovery was as great as 100%. The combined techniques were used to isolate IHNV from water samples taken from a river containing adult sockeye salmon (Oncorhynchus nerka) and from a hatchery pond containing adult spring chinook salmon (O. tshawytscha). The combination of these methods was effective in concentrating and detecting IHNV from water containing only three infectious particles per 10-L sample.
Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus.
Feduchi, E; Alonso, M A; Carrasco, L
The replication of herpes simplex virus type 1 (HSV-1) is not inhibited in either HeLa or HEp-2 cells treated with human alpha interferon (HuIFN-alpha), particularly when high multiplicities of infection are used. However, HuIFN-gamma partially inhibits HSV-1 translation in HEp-2 cells infected at low multiplicities. Under these conditions, the transcription of genes alpha 22, TK, and gamma 0 is greatly diminished. The combined addition of human tumor necrosis factor (TNF) and HuIFN-gamma to HEp-2 cells exerts a synergistic inhibition of HSV-1 translation. Cells treated with both cytokines continue synthesizing cellular proteins, even 20 h after HSV-1 infection. As little as 10 U of IFN-gamma per ml blocked HSV-1 DNA replication, provided that TNF was also present in the medium. Analyses of HSV-1 gene transcription suggest that the action of both TNF and IFN-gamma blocked a step that comes at or prior to early HSV-1 gene expression. This early step in HSV-1 replication inhibited by TNF and IFN-gamma occurs after virus attachment and entry into cells, since the internalization of radioactive HSV-1 virion particles was not blocked by the presence of the two cytokines. Therefore, we conclude that the synergistic action of TNF plus IFN-gamma affects a step in HSV-1 replication that comes after virus entry but before or at the transcription of immediate-early genes. Images PMID:2536838
[Novel treatments for hepatitis C virus infection in chronic kidney disease].
Fabrizi, Fabrizio; Messa, Piergiorgio
Recent evidence has been accumulated showing a negative impact of chronic hepatitis C virus infection on survival in patients with chronic kidney disease. Moreover, it appears that anti-HCV positive status has been associated with an increased risk of developing chronic kidney disease in the adult general population. These reports have emphasized the need for safe and effective therapies for hepatitis C virus infection in the chronic kidney disease population. Treatment of HCV has made considerable progress with the approval of interferon-free, direct-acting antiviral drug-based combination therapies among patients with intact kidneys; but a paucity of information exists regarding chronic kidney disease patients. The first published report on the antiviral treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 concerns the combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor); excellent safety and efficacy (sustained viral response, 94.3% 115/122) have been reached. In another study, the 3-D regimen (ombitasvir/ paritaprevir/ ritonavir/ dasabuvir with or without ribavirin) has been administered to CKD (stage 4-5) patients with genotype 1 (n=20); the rate of sustained viral response was excellent (90%, 18/20) and no patients discontinued treatment due to adverse events. Preliminary data on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89% (34/38), but the size of the study group (n=38 patients with end-stage renal disease) was small. Thus, the evidence in the medical literature concerning use of DAAs in CKD population is encouraging even if it has a preliminary nature. Also, several points need to be addressed regarding the use of DAAs in CKD population including their impact on survival, costs, and drug-drug interactions. PMID:27545640
Phylogenetic relationships of Iranian infectious hematopoietic necrosis virus of rainbow trout (Oncorhynchus mykiss) based on the glycoprotein gene
Adel, Milad; Amiri, Alireza Babaalian; Dada, Maryam; Kurath, Gael; Laktarashi, Bahram; Ghajari, Amrolah; Breyta, Rachel
Infectious hematopoietic necrosis virus (IHNV), a member of family Rhabdoviridae and genus Novirhabdoviridae, causes a highly lethal disease of salmon and trout. In Iran IHNV was first detected in 2001 on farms rearing rainbow trout (Oncorhynchus mykiss). To evaluate the genetic relationships of IHNV from northern and western Iran, the sequences of a 651-nt region of the glycoprotein gene were determined for two Iranian isolates. These sequences were analyzed to evaluate their genetic relatedness to worldwide isolates representing the five known genogroups of IHNV. Iranian isolates were most closely related to European isolates within the genogroup E rather than those of North American genogroups U, M and L, or the Asian genogroup J. It appears that Iranian IHNV was most likely introduced to Iran from a source in Europe by the movement of contaminated fish eggs.
Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone.
Folks, T M; Clouse, K A; Justement, J; Rabson, A; Duh, E; Kehrl, J H; Fauci, A S
Tumor necrosis factor alpha (TNF-alpha), also known as cachectin, was demonstrated to induce the expression of human immunodeficiency virus (HIV) in a chronically infected T-cell clone (ACH-2). Concentrations of recombinant TNF-alpha as low as 50 pg/ml induced a significant increase over background of HIV expression in the ACH-2 cells as determined by supernatant reverse transcriptase activity. The HIV-inducing effects of TNF-alpha could not be explained by toxic effects on the cells. In addition, both the uninfected parental cell line (A3.01) and the infected ACH-2 cells were shown to have high-affinity receptors for TNF-alpha. Transient-transfection experiments demonstrated that the inductive effects of TNF-alpha were due to specific activation of the HIV long terminal repeat. These studies provide evidence that TNF-alpha may play a role in the mechanisms of pathogenesis of HIV infection. Images PMID:2784570
Phylogenetic relationships of Iranian infectious hematopoietic necrosis virus of rainbow trout (Oncorhynchus mykiss) based on the glycoprotein gene.
Adel, Milad; Amiri, Alireza Babaalian; Dadar, Maryam; Breyta, Rachel; Kurath, Gael; Laktarashi, Bahram; Ghajari, Amrolah
Infectious hematopoietic necrosis virus (IHNV), a member of family Rhabdoviridae and genus Novirhabdoviridae, causes a highly lethal disease of salmon and trout. In Iran IHNV was first detected in 2001 on farms rearing rainbow trout (Oncorhynchus mykiss). To evaluate the genetic relationships of IHNV from northern and western Iran, the sequences of a 651-nt region of the glycoprotein gene were determined for two Iranian isolates. These sequences were analyzed to evaluate their genetic relatedness to worldwide isolates representing the five known genogroups of IHNV. Iranian isolates were most closely related to European isolates within the genogroup E rather than those of North American genogroups U, M and L, or the Asian genogroup J. It appears that Iranian IHNV was most likely introduced to Iran from a source in Europe by the movement of contaminated fish eggs. PMID:26602428
Spleen necrosis virus gag polyprotein is necessary for particle assembly and release but not for proteolytic processing.
Weaver, T A; Talbot, K J; Panganiban, A T
The nature of spleen necrosis virus pol gene expression and the role of gag and gag-pol polyproteins in virion assembly was investigated. The DNA sequence of the gag-pol junction revealed that the two genes occupy the same open reading frame but are separated by an in-frame amber stop codon. Biochemical analysis of gag-pol translational readthrough in vitro and in Escherichia coli suggests that, in a manner similar to that in other mammalian type C retroviruses, amber stop codon suppression is required for pol gene expression. Removal of the gag stop codon had little or no effect on synthesis or cleavage of the polyprotein but interrupted particle assembly. This block could be overcome by complementation with wild-type gag protein. Images PMID:2186174
Rapid detection of infectious hypodermal and hematopoietic necrosis virus (IHHNV) by real-time, isothermal recombinase polymerase amplification assay.
Xia, Xiaoming; Yu, Yongxin; Hu, Linghao; Weidmann, Manfred; Pan, Yingjie; Yan, Shuling; Wang, Yongjie
Infectious hypodermal and hematopoietic necrosis virus (IHHNV) causes mortality or runt deformity syndrome in penaeid shrimps and is responsible for significant economic losses in the shrimp aquaculture industry. Here, we describe a novel real-time isothermal recombinase polymerase amplification (RPA) assay developed for IHHNV detection. Using IHHNV plasmid standards and DNA samples from a variety of organisms, we evaluated the ability of the IHHNV-RPA assay to detect IHHNV based on analysis of its sensitivity, specificity, rapidity, and reproducibility. Probit analysis of eight independent experimental replicates indicated satisfactory performance of the RPA assay, which is sufficiently sensitive to detect as few as 4 copies of the IHHNV genome within 7 min at 39 °C with 95 % reliability. Therefore, this rapid RPA method has great potential for applications, either in field use or as a point of care diagnostic technique. PMID:25655264
Real-Time Quantitative PCR Assay for Monitoring of Nervous Necrosis Virus Infection in Grouper Aquaculture▿†
Kuo, Hsiao-Che; Wang, Ting-Yu; Chen, Peng-Peng; Chen, Young-Mao; Chuang, Hui-Ching; Chen, Tzong-Yueh
Viral nervous necrosis caused by nervous necrosis virus (NNV) exacts a high mortality and results in huge economic losses in grouper aquaculture in Taiwan. The present study developed a real-time quantitative PCR (qPCR) method for NNV monitoring. The assay showed a strong linear correlation (r2 = 0.99) between threshold cycle (CT) and RNA quantities, which allowed identification of infected groupers by the CT value and could be exploited to warn of NNV infection prior to an outbreak in grouper fish farms. Real-time qPCR also confirmed the copious content of NNV in grouper fin, similar to that in primary tissues; the result was verified by using in situ reverse transcription-PCR (RT-PCR). This indicated that grouper fin was a suitable sample for NNV detection, in a manner that could be relatively benign to the fish. The rapid spread of NNV infection to the entire population of affected farms was evident. The developed real-time qPCR method is rapid, highly sensitive, and applicable to routine high-throughput detection of large numbers of samples and has potential as a suitable tool for diagnostic, epidemiological, and genetic studies of grouper aquaculture. PMID:21233077
Expression of kidney injury molecule-1 (Kim-1) in relation to necrosis and apoptosis during the early stages of Cd-induced proximal tubule injury
Prozialeck, Walter C. Edwards, Joshua R.; Lamar, Peter C.; Liu, Jie; Vaidya, Vishal S.; Bonventre, Joseph V.
Cadmium (Cd) is a nephrotoxic industrial and environmental pollutant that causes a generalized dysfunction of the proximal tubule. Kim-1 is a transmembrane glycoprotein that is normally not detectable in non-injured kidney, but is up-regulated and shed into the urine during the early stages of Cd-induced proximal tubule injury. The objective of the present study was to examine the relationship between the Cd-induced increase in Kim-1 expression and the onset of necrotic and apoptotic cell death in the proximal tubule. Adult male Sprague-Dawley rats were treated with 0.6 mg (5.36 {mu}mol) Cd/kg, subcutaneously, 5 days per week for up to 12 weeks. Urine samples were analyzed for levels of Kim-1 and the enzymatic markers of cell death, lactate dehydrogenase (LDH) and alpha-glutathione-S-transferase ({alpha}-GST). In addition, necrotic cells were specifically labeled by perfusing the kidneys in situ with ethidium homodimer using a procedure that has been recently developed and validated in the Prozialeck laboratory. Cryosections of the kidneys were also processed for the immunofluorescent visualization of Kim-1 and the identification of apoptotic cells by TUNEL labeling. Results showed that significant levels of Kim-1 began to appear in the urine after 6 weeks of Cd treatment, whereas the levels of total protein, {alpha}-GST and LDH were not increased until 8-12 weeks. Results of immunofluorescence labeling studies showed that after 6 weeks and 12 weeks, Kim-1 was expressed in the epithelial cells of the proximal tubule, but that there was no increase in the number of necrotic cells, and only a modest increase in the number of apoptotic cells at 12 weeks. These results indicate that the Cd-induced increase in Kim-1 expression occurs before the onset of necrosis and at a point where there is only a modest level of apoptosis in the proximal tubule.
Management of diseases caused by thrips-transmitted tospoviruses in subsistence agriculture: the case of Peanut bud necrosis virus in India
Technology Transfer Automated Retrieval System (TEKTRAN)
Among the tospoviruses (genus Tospovirus, family Bunyaviridae) reported in India, Peanut bud necrosis virus is by far the most economically significant for tomato production in subsistence agriculture. Management of PBNV has been a challenge for farmers due to the broad host-range of PBNV and its ve...
Putative Promoters Isolated From Infectious Hypodermal and Hematopoietic Necrosis Virus of Shrimp Drive Expression of a Reporter Gene in Bacteria, Insect Cells, Fish Cells, and Shrimp
Technology Transfer Automated Retrieval System (TEKTRAN)
Infectious hypodermal and hematopoietic necrosis virus (IHHNV) of shrimp contains a linear single-stranded DNA genome of approximately 4.1 kb with three putative open reading frames (ORFs) namely, the left ORF, middle ORF and the right ORF on the same DNA strand. Whereas the left ORF codes for non-s...
A novel recombinant strain of Potato virus Y allows identification of a new viral genetic determinant of vein necrosis in tobacco
Technology Transfer Automated Retrieval System (TEKTRAN)
A novel Potato virus Y (PVY) isolate, L26, recovered from a Frontier potato line was initially typed as a PVYNTN strain using multiplex RT-PCR and serological assays. However, L26 induced mosaic and mild vein clearing symptoms in tobacco rather than vein necrosis characteristic of the PVY NTN strai...
Endogenous New World primate type C viruses isolated from owl monkey (Aotus trivirgatus) kidney cell line.
Todaro, G J; Sherr, C J; Sen, A; King, N; Daniel, M D; Fleckenstein, B
A type C virus (OMC-1) detected in a culture of owl monkey kidney cells resembled typical type C viruses morphologically, but was slightly larger than previously characterized mammalian type C viruses. OMC-1 can be transmitted to bat lung cells and cat embryo fibroblasts. The virions band at a density of 1.16 g/ml in isopycnic sucrose density gradients and contain reverse transcriptase and a 60-65S RNA genome composed of approximately 32S subunits. The reverse transcriptase is immunologically and biochemically distinct from the polymerases of othe retroviruses. Radioimmunoassays directed to the interspecies antigenic determinants of the major structure proteins of other type C viruses do not detect a related antigen in OMC-1. Nucleic acid hybridization experiments using labeled viral genomic RNA or proviral cDNA transcripts to normal cellular DNA of different species show that OMC-1 is an endogenous virus with multiple virogene copies (20-50 per haploid genome) present in normal owl monkey cells and is distinct from previously isolated type C and D viruses. Sequences related to the OMC-1 genome can be detected in other New World monkeys. Thus, similar to the Old World primates (e.g., baboons as a prototype), the New World monkeys contain endogenous type C viral genes that appear to have been transmitted in the primate germ line. Images PMID:76312
Complete genome sequence of acute viral necrosis virus associated with massive mortality outbreaks in the Chinese scallop, Chlamys farreri
Background Acute viral necrosis virus (AVNV) is the causative agent of a serious disease resulting in high mortality in cultured Chinese scallops, Chlamys farreri. We have sequenced and analyzed the complete genome of AVNV. Results The AVNV genome is a linear, double-stranded DNA molecule of 210,993 bp with a nucleotide composition of 38.5% G + C. A total of 123 open reading frames were predicted to encode functional proteins, ranging from 41 to 1,878 amino acid residues. The DNA sequence of AVNV is 97% identical to that of ostreid herpesvirus 1 (OsHV-1), and the amino acid sequences of the encoded proteins of these two viruses are 94-100% identical. The genomic organization of AVNV is similar to that of OsHV-1, and consists of two unique regions (170.4 kb and 3.4 kb, respectively), each flanked by two inverted repeats (7.6 kb and 10.2 kb, respectively), with a third unique region (1.5 kb) situated between the two internal repeats. Conclusions Our results indicate that AVNV is a variant of OsHV-1. The AVNV genome sequence provides information useful for understanding the evolution and divergence of OsHV-1 in marine molluscs. PMID:23566284
Transactivation of human immunodeficiency virus type 1 long terminal repeats by cell surface tumor necrosis factor alpha.
Tadmori, W; Mondal, D; Tadmori, I; Prakash, O
Tumor necrosis factor alpha (TNF-alpha) is expressed in secreted and cell surface (csTNF-alpha) forms by activated monocytic and T cells. In this report, we demonstrate that csTNF-alpha may predominantly regulate the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) activation in the promonocytic cell line U937 and in the Epstein-Barr virus-transformed B-cell line BH1. Anti-TNF-alpha antibody suppressed both the constitutive expression of the HIV-1 LTR in BH1 cells and the expression induced by phorbol 12-myristate 13-acetate in U937 cells. This suppression was found to be mediated via csTNF-alpha. No correlation between the HIV-1 LTR activation and the secretion of TNF-alpha was evident in these cell lines. Suppression of TNF-alpha secretion by cyclosporin A or by a serine protease inhibitor did not suppress the HIV-1 LTR activation. These observations suggest a novel biological role for csTNF-alpha in the immunopathogenesis of AIDS. PMID:1942242
Efficacy of an infectious hematopoietic necrosis (IHN) virus DNA vaccine in Chinook Oncorhynchus tshawytscha and sockeye O. nerka salmon
Garver, K.A.; LaPatra, S.E.; Kurath, G.
The level of protective immunity was determined for Chinook Oncorhynchus tshawytscha and sockeye/kokanee salmon (anadromous and landlocked) O. nerka following intramuscular vaccination with a DNA vaccine against the aquatic rhabdovirus, infectious hematopoietic necrosis virus (IHNV). A DNA vaccine containing the glycoprotein gene of IHNV protected Chinook and sockeye/kokanee salmon against waterborne or injection challenge with IHNV, and relative percent survival (RPS) values of 23 to 86% were obtained under a variety of lethal challenge conditions. Although this is significant protection, it is less than RPS values obtained in previous studies with rainbow trout (O. mykiss). In addition to the variability in the severity of the challenge and inherent host susceptibility differences, it appears that use of a cross-genogroup challenge virus strain may lead to reduced efficacy of the DNA vaccine. Neutralizing antibody titers were detected in both Chinook and sockeye that had been vaccinated with 1.0 and 0.1 ??g doses of the DNA vaccine, and vaccinated fish responded to viral challenges with higher antibody titers than mock-vaccinated control fish. ?? Inter-Research 2005.
Superior Orbital Fissure Syndrome and Ophthalmoplegia Caused by Varicella Zoster Virus with No Skin Eruption in a Patient Treated with Tumor Necrosis Alpha Inhibitor.
Jensen, Helene; Thomsen, Sidsel Thorup; Hansen, Stine Scott; Munksgaard, Signe Bruun; Lindelof, Mette
Varicella zoster virus lies dormant in the dorsal root ganglia after symptomatic chicken pox infection, usually in childhood. If the virus reactivates in the trigeminal ganglia, it can cause varicella zoster ophthalmicus, which can have severe ocular complications. We report a case of a 73-year-old woman in severe immunosuppression due to treatment with mycophenolate mofetil, glucocorticosteroids and a tumor necrosis factor alpha inhibitor. The reactivation caused superior orbital fissure syndrome, which has only rarely been described in relation to varicella zoster virus reactivation. In our case, the syndrome was seen along with severe encephalitis. PMID:26600786
Superior Orbital Fissure Syndrome and Ophthalmoplegia Caused by Varicella Zoster Virus with No Skin Eruption in a Patient Treated with Tumor Necrosis Alpha Inhibitor
Jensen, Helene; Thomsen, Sidsel Thorup; Hansen, Stine Scott; Munksgaard, Signe Bruun; Lindelof, Mette
Varicella zoster virus lies dormant in the dorsal root ganglia after symptomatic chicken pox infection, usually in childhood. If the virus reactivates in the trigeminal ganglia, it can cause varicella zoster ophthalmicus, which can have severe ocular complications. We report a case of a 73-year-old woman in severe immunosuppression due to treatment with mycophenolate mofetil, glucocorticosteroids and a tumor necrosis factor alpha inhibitor. The reactivation caused superior orbital fissure syndrome, which has only rarely been described in relation to varicella zoster virus reactivation. In our case, the syndrome was seen along with severe encephalitis. PMID:26600786
Comparison of in vitro growth characteristics of ten isolates of infectious hematopoietic necrosis virus
Mulcahy, D.; Pascho, R.J.; Jenes, C.K.
Ten isolates of infectious haematopoietic necrosis from salmonid fishes of different locations on the West Coast of North America from California to Alaska were compared by plaque size, single-step growth curves at 15 and 18 °C, rate of appearance of cytopathic effects in cell cultures, and growth over a range of temperatures. All isolates were distinguishable on the basis of each growth characteristic examined. The CO isolate from the Sacramento River drainage of California was the most singular of the 10 because of its diminutive plaque size and sensitivity to slightly elevated temperatures. The mean plaque diameter of the l0 isolates increased as the latitude of the geographic source of the isolate increased. Although the maximum titre obtained by all isolates was depressed at temperatures above approximately 18 °C, half of the isolates were not inhibited by temperatures as low as 0.5 °C. t.
The relationship between serology of hepatitis E virus with liver and kidney function in kidney transplant patients
Zeraati, Abbas Ali; Nazemian, Fatemeh; Takalloo, Ladan; Sahebkar, Amirhossein; Heidari, Elahe; Yaghoubi, Mohammad Ali
Although hepatitis E virus (HEV) is well known to cause acute hepatitis, there are reports showing that HEV may also be responsible for progression of acute to chronic hepatitis and liver cirrhosis in patients receiving organ transplantation. In this study, we aimed to evaluate the prevalence of HEV in patients with kidney transplantation. In this study, 110 patients with kidney transplantation were recruited, and anti-HEV IgG, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and estimated glomerular filtration rate (eGFR) in the first, third and sixth months after renal transplantation were measured. The mean serum anti-HEV IgG titers in the study participants was 1.36 (range 0.23 to 6.3). Twenty-three patients were found to be seropositive for HEV Ab defined as anti-HEV IgG titer > 1.1. The difference in liver and renal function tests (creatinine, eGFR, AST, ALT and ALP) at different intervals was not significant between patients with HEV Ab titers higher and lower than 1.1 (p > 0.05). However, an inverse correlation was observed between HEV Ab and eGFR values in the first (p = 0.047, r = -0.21), third (p = 0.04, r = -0.20) and sixth (p = 0.04, r = -0.22) months after renal transplantation in patients with HEV Ab < 1.1 but not in the subgroup with HEV Ab > 1.1. Also, a significant correlation between age and HEV Ab levels was found in the entire study population (p = 0.001, r = 0.33). Our findings showed a high prevalence of seropositivity for anti-HEV IgG in patients receiving renal transplants. However, liver and renal functions were not found to be significantly different seropositive and seronegative patients by up to 6 months post-transplantation. PMID:27366144
The relationship between serology of hepatitis E virus with liver and kidney function in kidney transplant patients.
Zeraati, Abbas Ali; Nazemian, Fatemeh; Takalloo, Ladan; Sahebkar, Amirhossein; Heidari, Elahe; Yaghoubi, Mohammad Ali
Although hepatitis E virus (HEV) is well known to cause acute hepatitis, there are reports showing that HEV may also be responsible for progression of acute to chronic hepatitis and liver cirrhosis in patients receiving organ transplantation. In this study, we aimed to evaluate the prevalence of HEV in patients with kidney transplantation. In this study, 110 patients with kidney transplantation were recruited, and anti-HEV IgG, creatinine, alanine transaminase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and estimated glomerular filtration rate (eGFR) in the first, third and sixth months after renal transplantation were measured. The mean serum anti-HEV IgG titers in the study participants was 1.36 (range 0.23 to 6.3). Twenty-three patients were found to be seropositive for HEV Ab defined as anti-HEV IgG titer > 1.1. The difference in liver and renal function tests (creatinine, eGFR, AST, ALT and ALP) at different intervals was not significant between patients with HEV Ab titers higher and lower than 1.1 (p > 0.05). However, an inverse correlation was observed between HEV Ab and eGFR values in the first (p = 0.047, r = -0.21), third (p = 0.04, r = -0.20) and sixth (p = 0.04, r = -0.22) months after renal transplantation in patients with HEV Ab < 1.1 but not in the subgroup with HEV Ab > 1.1. Also, a significant correlation between age and HEV Ab levels was found in the entire study population (p = 0.001, r = 0.33). Our findings showed a high prevalence of seropositivity for anti-HEV IgG in patients receiving renal transplants. However, liver and renal functions were not found to be significantly different seropositive and seronegative patients by up to 6 months post-transplantation. PMID:27366144
Experimental Transmission of Infectious Pancreatic Necrosis Virus from the Blue Mussel, Mytilus edulis, to Cohabitating Atlantic Salmon (Salmo salar) Smolts
Pietrak, Michael R.; Bricknell, Ian
Integrated multitrophic aquaculture (IMTA) reduces the environmental impacts of commercial aquaculture systems by combining the cultivation of fed species with extractive species. Shellfish play a critical role in IMTA systems by filter-feeding particulate-bound organic nutrients. As bioaccumulating organisms, shellfish may also increase disease risk on farms by serving as reservoirs for important finfish pathogens such as infectious pancreatic necrosis virus (IPNV). The ability of the blue mussel (Mytilus edulis) to bioaccumulate and transmit IPNV to naive Atlantic salmon (Salmo salar) smolts was investigated. To determine the ability of mussels to filter and accumulate viable IPNV, mussels were held in water containing log 4.6 50% tissue culture infective dose(s) (TCID50) of the West Buxton strain of IPNV ml−1. Viable IPNV was detected in the digestive glands (DGs) of IPNV-exposed mussels as early as 2 h postexposure. The viral load in mussel DG tissue significantly increased with time and reached log 5.35 ± 0.25 TCID50 g of DG tissue−1 after 120 h of exposure. IPNV titers never reached levels that were significantly greater than that in the water. Viable IPNV was detected in mussel feces out to 7 days postdepuration, and the virus persisted in DG tissues for at least 18 days of depuration. To determine whether IPNV can be transmitted from mussels to Atlantic salmon, IPNV-exposed mussels were cohabitated with naive Atlantic salmon smolts. Transmission of IPNV did occur from mussels to smolts at a low frequency. The results demonstrate that a nonenveloped virus, such as IPNV, can accumulate in mussels and be transferred to naive fish. PMID:23872575
A Preliminary Study Into the Significance of Intrarenal Reflux in BK Virus Nephropathy After Kidney Transplantation
Kawanishi, Kunio; Honda, Kazuho; Koike, Junki; Hattori, Motoshi; Fuchinoue, Shouhei; Tanabe, Kazunari; Oda, Hideaki; Nagashima, Yoji
Background The BK virus typically colonizes the lower urinary tract and is the causative agent in BK virus nephropathy (BKVN), which can progress to allograft dysfunction and graft loss. Urinary reflux in kidney allografts is induced by vesicoureteral reflux or disturbances in intrarenal reflux (IRR), believed to be associated with BKVN. This study was designed to elucidate the relationship between BKVN and IRR. Methods We examined 30 renal transplant recipients histologically diagnosed with BKVN using anti-Simian virus 40 immunohistochemistry and 60 clinically matched control recipients. The BKVN patients were divided into stable (n = 12) and progressive (n = 18) groups according to allograft kidney function 1 year after diagnosis. Histological rejection scores according to the pathological classification of rejection in renal allografts (Banff classification), histological BKVN stages, and histological polyomavirus load levels (pvl) proposed by the Banff working group were evaluated. The IRR was quantified by histological reflux scores defined with retention and reflux of immunostained Tamm-Horsfall protein in renal tubules and glomeruli. Results Higher reflux scores were observed in the BKVN group compared with that in the control group. No differences in clinical parameters were observed between the BKVN and control groups. Reflux scores and pvl were significantly higher in the progressive group than in the stable BKVN group with no significant difference in BK stage observed between groups. Reflux scores were found to be significantly correlated with pvl. Conclusions Our preliminary study suggested that IRR might be a predisposing and prognostic factor in BKVN.
Nucleic Acid of Rubella Virus and Its Replication in Hamster Kidney Cells
Sedwick, W. David; Sokol, Frantisek
Ribonucleic acid (RNA) has been isolated from partially purified rubella virus preparations and fractionated by rate zonal centrifugation in sucrose density gradients. The bulk of the RNA sedimented as a sharp band with a sedimentation coefficient of 38S. Rubella virus RNA appears to be single-stranded on the basis of its sensitivity to the degrading action of ribonuclease. Fractionation by precipitation with 1 m NaCl, followed by chromatography on cellulose columns, and by rate zonal centrifugation in sucrose density gradients of labeled RNA isolated from actinomycin D-treated and infected baby hamster kidney cells revealed the presence of the following virus-specific types of RNA: (i) single-stranded RNA with a heterogeneous sedimentation pattern, the 38S viral RNA becoming the predominant species only after long periods of labeling late after infection; (ii) double-stranded RNA with a sedimentation coefficient of 20S; (iii) RNA apparently composed of 20S double-stranded RNA and single-stranded branches. On the basis of their properties, the last two species were tentatively identified as the replicative form and the replicative intermediate of rubella virus RNA. Rubella virus RNA was infectious. PMID:5465639
The coat protein of Alternanthera mosaic virus is the elicitor of a temperature-sensitive systemic necrosis in Nicotiana benthamiana, and interacts with a host boron transporter protein
Lim, Hyoun-Sub; Nam, Jiryun; Seo, Eun-Young; Nam, Moon; Vaira, Anna Maria; Bae, Hanhong; Jang, Chan-Yong; Lee, Cheol Ho; Kim, Hong Gi; Roh, Mark; Hammond, John
Different isolates of Alternanthera mosaic virus (AltMV; Potexvirus), including four infectious clones derived from AltMV-SP, induce distinct systemic symptoms in Nicotiana benthamiana. Virus accumulation was enhanced at 15 °C compared to 25 °C; severe clone AltMV 3-7 induced systemic necrosis (SN) and plant death at 15 °C. No interaction with potexvirus resistance gene Rx was detected, although SN was ablated by silencing of SGT1, as for other cases of potexvirus-induced necrosis. Substitution of AltMV 3-7 coat protein (CP{sub SP}) with that from AltMV-Po (CP{sub Po}) eliminated SN at 15 °C, and ameliorated symptoms in Alternanthera dentata and soybean. Substitution of only two residues from CP{sub Po} [either MN(13,14)ID or LA(76,77)IS] efficiently ablated SN in N. benthamiana. CP{sub SP} but not CP{sub Po} interacted with Arabidopsis boron transporter protein AtBOR1 by yeast two-hybrid assay; N. benthamiana homolog NbBOR1 interacted more strongly with CP{sub SP} than CP{sub Po} in bimolecular fluorescence complementation, and may affect recognition of CP as an elicitor of SN. - Highlights: • Alternanthera mosaic virus CP is an elicitor of systemic necrosis in N. benthamiana. • Virus-induced systemic necrosis is enhanced at 15 °C compared to 25 °C. • Induction of systemic necrosis is dependent on as few as two CP amino acid residues. • These residues are at subunit interfaces within the same turn of the virion helix. • Inducer/non-inducer CPs interact differentially with a boron transporter protein.
Genetic Diversity of the Coat Protein of Olive Mild Mosaic Virus (OMMV) and Tobacco Necrosis Virus D (TNV-D) Isolates and Its Structural Implications
Varanda, Carla M. R.; Machado, Marco; Martel, Paulo; Nolasco, Gustavo; Clara, Maria I. E.; Félix, Maria R.
The genetic variability among 13 isolates of Olive mild mosaic virus (OMMV) and of 11 isolates of Tobacco necrosis virus D (TNV-D) recovered from Olea europaea L. samples from various sites in Portugal, was assessed through the analysis of the coat protein (CP) gene sequences. This gene was amplified through reverse transcriptase polymerase chain reaction (RT-PCR), cloned, and 5 clone sequences of each virus isolate, were analysed and compared, including sequences from OMMV and TNV-D isolates originally recovered from different hosts and countries and available in the GenBank, totalling 131 sequences. The encoded CP sequences consisted of 269 amino acids (aa) in OMMV and 268 in TNV-D. Comparison of the CP genomic and amino acid sequences of the isolates showed a very low variability among OMMV isolates, 0.005 and 0.007, respectively, as well as among TNV-D isolates, 0.006 and 0.008. The maximum nucleotide distances of OMMV and TNV-D sequences within isolates were also low, 0.013 and 0.031, respectively, and close to that found between isolates, 0.018 and 0.034, respectively. In some cases, less variability was found in clone sequences between isolates than in clone sequences within isolates, as also shown through phylogenetic analysis. CP aa sequence identities among OMMV and TNV-D isolates ranged from 84.3% to 85.8%. Comparison between the CP genomic sequences of the two viruses, showed a relatively low variability, 0.199, and a maximum nucleotide distance between isolates of 0.411. Analysis of comparative models of OMMV and TNV-D CPs, showed that naturally occurring substitutions in their respective sequences do not seem to cause significant alterations in the virion structure. This is consistent with a high selective pressure to preserve the structure of viral capsid proteins. PMID:25350108
Epidemiology, clinical characteristics, and management of chronic kidney disease in human immunodeficiency virus-infected patients
Ando, Minoru; Yanagisawa, Naoki
Antiretroviral therapy has markedly reduced acquired immune deficiency syndrome-related deaths and opportunistic infectious diseases. This has resulted in prolonged survival of individuals infected with the human immunodeficiency virus (HIV). However, this improvement in survival has been accompanied by an increase in the incidence of chronic kidney disease (CKD) and end-stage renal disease. CKD is now epidemic among HIV-infected populations in both Western and Eastern countries. Risk factors associated with CKD in HIV-infected populations include aging, hypertension, diabetes mellitus, co-infection with hepatitis C virus, a low CD4 cell count, and a high HIV viral load. Clinical experience has shown that HIV-infected individuals often have one or more concurrent risk factors for CKD. The cumulative effect of multiple risk factors on the development of CKD should be noted in this population. Glomerular disease directly related to HIV infection, so-called HIV-associated nephropathy, remains an important cause of CKD among a limited HIV population of African descent, but is less likely to be common among other urban HIV populations. The impact of exposure to nephrotoxic antiretroviral agents on the development of kidney disease is both an old and a new concern. In particular, the association of tenofovir with kidney tubular injury has been an area of great interest. The findings regarding tenofovir's adverse effect on long-term kidney function vary among studies. The early identification and treatment of CKD is recommended for reducing the burden of patients requiring dialysis in HIV-infected populations. Periodic monitoring of urinary concentrations of albumin, protein, and tubular injury markers such as low-molecular-weight proteins may be useful for the early diagnosis of patients at risk for incident CKD. This review focuses on recent epidemiology, clinical characteristics, and management of CKD in a contemporary HIV-infected population. PMID:26167463
De Novo Belatacept in a Human Immunodeficiency Virus-Positive Kidney Transplant Recipient.
Cohen, E A; Mulligan, D; Kulkarni, S; Tichy, E M
Benefits of belatacept-based immunosuppressive regimens in human immunodeficiency virus (HIV)-positive renal transplant recipients include avoidance of drug interactions between calcineurin inhibitors and highly active antiretroviral agents and decreased likelihood or severity of nonimmune toxicities such as new-onset diabetes after transplant, hyperlipidemia and hypertension. We report a successful case of de novo belatacept at >18 mo from transplant in an HIV-positive black man aged 50 years who received his first transplant from a living related kidney donor. To our knowledge, this case is the first reported of belatacept use in an HIV-positive renal transplant recipient. PMID:27137752
Evaluation of a Subunit Vaccine to Infectious Hematopoietic Necrosis (IHN) Virus, 1984 FY Annual Report.
Leong, JoAnn Ching
A prototype subunit vaccine to IHN virus is being developed by recombinant DNA techniques. The techniques involve the isolation and characterization of the glycoprotein gene, which encodes the viral protein responsible for inducing a protective immune response in fish. The viral glycoprotein gene has been cloned and a restriction map of the cloned gene has been prepared. Preliminary DNA sequence analysis of the cloned gene has been initiated so that manipulation of the gene for maximum expression in appropriate plasmid vectors is possible. A recombinant plasmid containing the viral gene inserted in the proper orientation adjacent to a very strong lambda promoter and ribosome binding site has been constructed. Evaluation of this recombinant plasmid for gene expression is being conducted. Immunization trials with purified viral glycoprotein indicate that fish are protected against lethal doses of IHNV after immersion and intraperitoneal methods of immunization. In addition, cross protection immunization trials indicate that Type 2 and Type 1 IHN virus produce glycoproteins that are cross-protective.
Elevated plasma tumor necrosis factor-α receptor 2 and resistin are associated with increased incidence of kidney function decline in Chinese adults.
Liu, Gang; Deng, Yueyi; Sun, Liang; Ye, Xingwang; Yao, Pang; Hu, Yao; Wang, Feijie; Ma, Yiwei; Li, Huaixing; Liu, Yong; Sun, Qi; Lin, Xu
Adipokines and inflammatory markers have been linked to kidney disease in animal models; however, evidence from prospective human studies is sparse. Recruited from Beijing and Shanghai in 2005, a total number of 2220 non-institutionalized Chinese individuals aged 50-70 years with baseline estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m(2) were prospectively followed for 6 years. Plasma levels of resistin, retinol-binding protein 4 (RBP4), interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-α receptor 2 (TNF-R2) were determined at baseline. Kidney function decrease was assessed by measurements of eGFR over 6 years. Incident-reduced eGFR was defined as the onset of eGFR <60 mL/min/1.73 m(2), according to the Modification of Diet in Renal Disease Study Equation for Chinese. During the 6 years of follow-up, 333 (15.0 %) participants had incident-reduced eGFR. Each 1 standard deviation elevated concentration of resistin [relative risk (RR) 1.10; 95 % CI 1.00-1.24] and TNFR-2 (RR 1.30; 95 % CI 1.13-1.49) at baseline were significantly associated with a higher risk of incident-reduced eGFR. Comparing the highest with the lowest quartiles, the RR of incident-reduced eGFR was 1.43 (95 % CI 1.01-2.03) for resistin and 2.03 (95 % CI 1.41-2.93) for TNF-R2 (both P trend < 0.05) after adjustment for baseline demographic characteristics, lifestyle behaviors, BMI, plasma lipid profile, hypertension, and diabetes. These associations remained significant when further controlling for levels of RBP4, IL-6, and CRP, none of which was significantly associated with the risk of incident-reduced eGFR. In this prospective cohort study, elevated levels of resistin and TNF-R2, but not other adipokines and inflammatory markers, were independently associated with a greater risk of kidney function decline in middle-aged and elderly Chinese. PMID:26590599
Isolation and adaptation of bovine herpes virus Type 1 in embryonated chicken eggs and in Madin–Darby bovine kidney cell line
Samrath, Devprabha; Shakya, Sanjay; Rawat, Nidhi; Gilhare, Varsha Rani; Singh, Fateh
Aim: Objective of the present study was to isolate bovine herpes virus Type 1 (BHV-1) from semen of infected bull and to adapt it onto embryonated eggs and Madin–Darby bovine kidney (MDBK) cell line. Further, the virus was identified by agar gel immunodiffusion (AGID) test. Materials and Methods: Semen samples were collected from five BHV-1 positive bulls previously confirmed for the presence of antibodies against BHV-1 using avidin-biotin enzyme linked immunosorbent assay test. The virus from semen samples was adapted in chorioallantoic membrane (CAM) of 11-day-old embryonated chickens eggs and in MDBK cell line. The presence of BHV-1 in infected CAM and cell culture fluid was confirmed by AGID test. Results: Virus infected CAM showed edema, congestion and thickening at first passage level. Small foci ranged from 1 to 2 mm in diameter, scattered all over the membrane were observed at first passage. More severe changes were observed in CAM after serial passaging. The large pock lesions, round in shape with opaque raised edge and depressed gray central area of necrosis ranged from 3 to 5 mm in diameter were developed at fourth passage. Blind passages in MDBK cell culture were made. The MDBK cell line at second passage level showed characteristic cytopathic effect viz. rounding of cells with shrinkage, followed by aggregation or clumping of cells which progressed rapidly and appeared as "bunch of grapes" at 72 h post inoculation. Few cells become elongated when compared with uninfected controls. A homogenate of CAM with distinct pock lesions and infected cell culture fluid developed precipitation line within 48 h against specific anti-BHV-1 immune serum by AGID test. Conclusion: BHV-1 was easily adapted in CAM of chicken embryos and in MDBK cell line. Virus infected CAM and cell culture fluid showed precipitin band by AGID test. PMID:27051213
Evaluation of the tepary bean (Phaseolus acutifolius) diversity panel for response to the NL 3 strain of Bean Common Mosaic Necrosis Virus (BCMNV) and for biological nitrogen fixation with Bradyrhizobium strains
Technology Transfer Automated Retrieval System (TEKTRAN)
Aphid-transmitted Bean Common Mosaic Necrosis Virus (BCMNV) and Bean Common Mosaic Virus (BCMV) are potyviruses that are seed transmitted in tepary bean. Developing resistance to these viruses will be critical for expanding production in areas where they are endemic. Biological nitrogen fixation (BN...
Development of a subunit vaccine for infectious pancreatic necrosis virus using a baculovirus insect/larvae system
Shivappa, R.B.; McAllister, P.E.; Edwards, G.H.; Santi, N.; Evensen, O.; Vakharia, V.N.
Various attempts to develop a vaccine against infectious pancreatic necrosis virus (IPNV) have not yielded consistent results. Thus, at present, no commercial vaccine is available that can be used with confidence to immunize fry of salmon and trout. We generated a cDNA clone of the large genome segment A of an IPNV Sp strain and expressed all structural protein genes in insect cells and larvae using a baculovirus expression system. Green fluorescent protein was also co-expressed as a reporter molecule. High yields of IPNV proteins were obtained and the structural proteins self assembled to form virus-like particles (VLPs). We tested the immunogenicity of the putative VLP antigen in immersion vaccine experiments (two concentrations) in rainbow trout (Oncorhynchus mykiss) fry, and by intraperitoneal immunisation of Atlantic salmon (Salmo salar) pre-smolts using an oil adjuvant formulation. Rainbow trout were challenged by immersion using either the Sp or the VR-299 strain of IPNV two or three weeks post-vaccination, while Atlantic salmon were bath challenged with Sp strain after two months, after parr-smolt transformation. In the rainbow trout fry challenged two weeks post-immunization, cumulative mortality rates three weeks post challenge were 14 % in the fry that had received the highest dose versus 8 % in the control groups. No indication of protection was seen in repeated trials using a lower dose of antigen and challenge three weeks post-immunisation. The cumulative mortality rate of intraperitoneally immunised Atlantic salmon post-smolts four weeks post challenge was lower (56 %) than in the control fish (77 %), showing a dose-response pattern.
Arabidopsis TTR1 causes LRR-dependent lethal systemic necrosis, rather than systemic acquired resistance, to Tobacco ringspot virus.
Nam, Moon; Koh, Serry; Kim, Sung Uk; Domier, Leslie L; Jeon, Jae Heung; Kim, Hong Gi; Lee, Su-Heon; Bent, Andrew F; Moon, Jae Sun
Most Arabidopsis ecotypes display tolerance to the Tobacco ringspot virus (TRSV), but a subset of Arabidopsis ecotypes, including Estland (Est), develop lethal systemic necrosis (LSN), which differs from the localized hypersensitive responses (HRs) or systemic acquired resistance (SAR) characteristic of incompatible reactions. Neither viral replication nor the systemic movement of TRSV was restricted in tolerant or sensitive Arabidopsis ecotypes; therefore, the LSN phenotype shown in the sensitive ecotypes might not be due to viral accumulation. In the present study, we identified the Est TTR1 gene (tolerance to Tobacco ringspot virus 1) encoding a TIR-NBS-LRR protein that controls the ecotype-dependent tolerant/sensitive phenotypes by a map-based cloning method. The tolerant Col-0 ecotype Arabidopsis transformed with the sensitive Est TTR1 allele developed an LSN phenotype upon TRSV infection, suggesting that the Est TTR1 allele is dominant over the tolerant ttr1 allele of Col-0. Multiple sequence alignments of 10 tolerant ecotypes from those of eight sensitive ecotypes showed that 10 LRR amino acid polymorphisms were consistently distributed across the TTR1/ttr1 alleles. Site-directed mutagenesis of these amino acids in the LRR region revealed that two sites, L956S and K1124Q, completely abolished the LSN phenotype. VIGS study revealed that TTR1 is dependent on SGT1, rather than EDS1. The LSN phenotype by TTR1 was shown to be transferred to Nicotiana benthamiana, demonstrating functional conservation of TTR1 across plant families, which are involved in SGT-dependent defense responses, rather than EDS1-dependent signaling pathways. PMID:22057987
Arabidopsis TTR1 Causes LRR-Dependent Lethal Systemic Necrosis, rather than Systemic Acquired Resistance, to Tobacco Ringspot Virus
Nam, Moon; Koh, Serry; Kim, Sung Uk; Domier, Leslie L.; Jeon, Jae Heung; Kim, Hong Gi; Lee, Su-Heon; Bent, Andrew F.; Moon, Jae Sun
Most Arabidopsis ecotypes display tolerance to the Tobacco ringspot virus (TRSV), but a subset of Arabidopsis ecotypes, including Estland (Est), develop lethal systemic necrosis (LSN), which differs from the localized hypersensitive responses (HRs) or systemic acquired resistance (SAR) characteristic of incompatible reactions. Neither viral replication nor the systemic movement of TRSV was restricted in tolerant or sensitive Arabidopsis ecotypes; therefore, the LSN phenotype shown in the sensitive ecotypes might not be due to viral accumulation. In the present study, we identified the Est TTR1 gene (tolerance to Tobacco ringspot virus 1) encoding a TIR-NBS-LRR protein that controls the ecotype-dependent tolerant/sensitive phenotypes by a map-based cloning method. The tolerant Col-0 ecotype Arabidopsis transformed with the sensitive Est TTR1 allele developed an LSN phenotype upon TRSV infection, suggesting that the Est TTR1 allele is dominant over the tolerant ttr1 allele of Col-0. Multiple sequence alignments of 10 tolerant ecotypes from those of eight sensitive ecotypes showed that 10 LRR amino acid polymorphisms were consistently distributed across the TTR1/ttr1 alleles. Site-directed mutagenesis of these amino acids in the LRR region revealed that two sites, L956S and K1124Q, completely abolished the LSN phenotype. VIGS study revealed that TTR1 is dependent on SGT1, rather than EDS1. The LSN phenotype by TTR1 was shown to be transferred to Nicotiana benthamiana, demonstrating functional conservation of TTR1 across plant families, which are involved in SGT-dependent defense responses, rather than EDS1-dependent signaling pathways. PMID:22057987
Infectious pancreatic necrosis virus (IPNV) strain with genetic properties associated with low pathogenicity at Finnish fish farms.
Eriksson-Kallio, Anna Maria; Holopainen, Riikka; Viljamaa-Dirks, Satu; Vennerström, Pia; Kuukka-Anttila, Hanna; Koski, Perttu; Gadd, Tuija
Infectious pancreatic necrosis (IPN) is a contagious viral disease of fish that causes economic losses in aquaculture worldwide. In Finland, IPN virus (IPNV) has been isolated since 1987 from adult fish showing no signs of clinical disease at fish farms located in the coastal areas of the Baltic Sea. The inland area of Finland, however, remained free of IPN until 2012, when fish on several rainbow trout farms were diagnosed IPNV-positive. The fish mortalities detected at the farms were low, but clinical signs and histopathological changes typical for IPNV infection were seen in juvenile salmonids. IPNV was isolated at high water temperatures up to 22°C. In 2013 and 2014, IPNV detections continued at inland farms, indicating that infections have spread. The aim of this study was to describe the epidemiology of the outbreak and to characterise the Finnish inland IPNV isolates using histopathological, immunohistochemical and genetic approaches. In order to determine the epidemiological origin of the inland IPNV infections, the partial viral capsid protein (VP2) gene sequences of the inland IPNV isolates were compared with the sequences of the isolates from the coastal farms. Based on the genetic analysis, the inland isolates belong to IPNV Genogroup 2 (Serotype A3/Ab), and the origin of the isolates appears to be one or several coastal fish farms. PMID:26865232
Screening and analysis of genes expressed upon infection of broad bean with Clover yellow vein virus causing lethal necrosis.
Nakahara, Kenji S; Kitazawa, Hiroaki; Atsumi, Go; Choi, Sun Hee; Suzuki, Yuji; Uyeda, Ichiro
Clover yellow vein virus (ClYVV) causes lethal systemic necrosis in legumes, including broad bean (Vicia faba) and pea (Pisum sativum). To identify host genes involved in necrotic symptom expression after ClYVV infection, we screened cDNA fragments in which expression was changed in advance of necrotic symptom expression in broad bean (V. faba cv. Wase) using the differential display technique and secondarily with Northern blot analysis. Expression changes were confirmed in 20 genes, and the six that exhibited the most change were analyzed further. These six genes included a gene that encodes a putative nitrate-induced NOI protein (VfNOI), and another was homologous to an Arabidopsis gene that encodes a glycine- and proline-rich protein GPRP (VfGPRP). We recently reported that necrotic symptom development in ClYVV-infected pea is associated with expression of salicylic acid (SA)-dependent pathogenesis-related (PR) proteins and requires SA-dependent host responses. Interestingly, VfNOI and VfGPRP expression was correlated with that of the putative SA-dependent PR proteins in ClYVV-infected broad bean. However, broad bean infected with a recombinant ClYVV expressing the VfGPRP protein showed weaker symptoms and less viral multiplication than that infected with ClYVV expressing the GFP protein. These results imply that VfGPRP plays a role in defense against ClYVV rather than in necrotic symptom expression. PMID:21767375
RAPD markers as predictors of infectious hypodermal and hematopoietic necrosis virus (IHHNV) resistance in shrimp (Litopenaeus stylirostris).
Hizer, Suzanne E; Dhar, Arun K; Klimpel, Kurt R; Garcia, Denise K
Random amplified polymorphic DNA (RAPD) fingerprints of two shrimp populations (Litopenaeus stylirostris) were compared to find genetic marker(s) that may be associated with infectious hypodermal and hematopoietic necrosis virus (IHHNV) resistance or susceptibility. Of the 100 10-mer random primers and 100 intersimple-sequence repeat (ISSR) primers screened, five provided markers specific to the Super Shrimp population and three provided markers specific to the wild caught population. The two populations were further characterized for relative viral load (reported as cycle threshold, CT) using real-time quantitative PCR with primers specific to the IHHNV genome. The beta-actin gene was amplified to serve as a control for normalization of the IHHNV viral load. The mean viral load was significantly lower (C(T) = 34.58; equivalent to 3.3 x 10(1) copies of IHHNV genome/ng DNA) in Super Shrimp than in the wild caught population (CT = 23.49; equivalent to 4.2 x 10(4) copies/ng DNA; P < 0.001; CT values are inversely related to viral load). A preliminary prediction model was created with Classification and Regression Tree (CART) software (Salford Systems, San Diego, Calif.), where the resultant decision tree uses the presence or absence of seven RAPD markers as predictors of the relative viral load. PMID:11908650
Modelling Infectious Hematopoietic Necrosis Virus Dispersion from Marine Salmon Farms in the Discovery Islands, British Columbia, Canada.
Foreman, Michael G G; Guo, Ming; Garver, Kyle A; Stucchi, Dario; Chandler, Peter; Wan, Di; Morrison, John; Tuele, Darren
Finite volume ocean circulation and particle tracking models are used to simulate water-borne transmission of infectious hematopoietic necrosis virus (IHNV) among Atlantic salmon (Salmo salar) farms in the Discovery Islands region of British Columbia, Canada. Historical simulations for April and July 2010 are carried out to demonstrate the seasonal impact of river discharge, wind, ultra-violet (UV) radiation, and heat flux conditions on near-surface currents, viral dispersion and survival. Numerical particles released from infected farm fish in accordance with IHNV shedding rates estimated through laboratory experiments are dispersed by model oceanic flows. Viral particles are inactivated by ambient UV radiation levels and by the natural microbial community at rates derived through laboratory studies. Viral concentration maps showing temporal and spatial changes are produced and combined with lab-determined minimum infectious dosages to estimate the infective connectivity among farms. Results demonstrate that neighbouring naïve farms can become exposed to IHNV via water-borne transport from an IHNV diseased farm, with a higher risk in April than July, and that many events in the sequence of farm outbreaks in 2001-2002 are consistent with higher risks in our farm connectivity matrix. Applications to other diseases, transfers between farmed and wild fish, and the effect of vaccinations are also discussed. PMID:26114643
Modelling Infectious Hematopoietic Necrosis Virus Dispersion from Marine Salmon Farms in the Discovery Islands, British Columbia, Canada
Foreman, Michael G. G.; Guo, Ming; Garver, Kyle A.; Stucchi, Dario; Chandler, Peter; Wan, Di; Morrison, John; Tuele, Darren
Finite volume ocean circulation and particle tracking models are used to simulate water-borne transmission of infectious hematopoietic necrosis virus (IHNV) among Atlantic salmon (Salmo salar) farms in the Discovery Islands region of British Columbia, Canada. Historical simulations for April and July 2010 are carried out to demonstrate the seasonal impact of river discharge, wind, ultra-violet (UV) radiation, and heat flux conditions on near-surface currents, viral dispersion and survival. Numerical particles released from infected farm fish in accordance with IHNV shedding rates estimated through laboratory experiments are dispersed by model oceanic flows. Viral particles are inactivated by ambient UV radiation levels and by the natural microbial community at rates derived through laboratory studies. Viral concentration maps showing temporal and spatial changes are produced and combined with lab-determined minimum infectious dosages to estimate the infective connectivity among farms. Results demonstrate that neighbouring naïve farms can become exposed to IHNV via water-borne transport from an IHNV diseased farm, with a higher risk in April than July, and that many events in the sequence of farm outbreaks in 2001-2002 are consistent with higher risks in our farm connectivity matrix. Applications to other diseases, transfers between farmed and wild fish, and the effect of vaccinations are also discussed. PMID:26114643
Protective immunity and lack of histopathological damage two years after DNA vaccination against infectious hematopoietic necrosis virus in trout
Kurath, Gael; Garver, Kyle A.; Corbeil, Serge; Elliott, Diane G.; Anderson, Eric D.; LaPatra, Scott E.
The DNA vaccine pIHNw-G encodes the glycoprotein of the fish rhabdovirus infectious hematopoietic necrosis virus (IHNV). Vaccine performance in rainbow trout was measured 3, 6, 13, 24, and 25 months after vaccination. At three months all fish vaccinated with 0.1 μg pIHNw-G had detectable neutralizing antibody (NAb) and they were completely protected from lethal IHNV challenge with a relative percent survival (RPS) of 100% compared to control fish. Viral challenges at 6, 13, 24, and 25 months post-vaccination showed protection with RPS values of 47–69%, while NAb seroprevalence declined to undetectable levels. Passive transfer experiments with sera from fish after two years post-vaccination were inconsistent but significant protection was observed in some cases. The long-term duration of protection observed here defined a third temporal phase in the immune response to IHNV DNA vaccination, characterized by reduced but significant levels of protection, and decline or absence of detectable NAb titers. Examination of multiple tissues showed an absence of detectable long-term histopathological damage due to DNA vaccination.
Nanogram quantities of a DNA vaccine protect rainbow trout fry against heterologous strains of infectious hematopoietic necrosis virus
Corbeil, S.; LaPatra, S.E.; Anderson, E.D.; Kurath, G.
The efficacy of a DNA vaccine containing the glycoprotein gene of infectious hematopoietic necrosis virus (IHNV), a rhabdovirus affecting trout and salmon, was investigated. The minimal dose of vaccine required, the protection against heterologous strains, and the titers of neutralizing antibodies produced were used to evaluate the potential of the vaccine as a control pharmaceutical. Results indicated that a single dose of as little as 1–10 ng of vaccine protected rainbow trout fry against waterborne challenge by IHNV. An optimal dose of 100 ng per fish was selected to assure strong protection under various conditions. Neutralizing antibody titers were detected in fish vaccinated with concentrations of DNA ranging from 5 to 0.01 μg. Furthermore, the DNA vaccine protected fish against a broad range of viral strains from different geographic locations, including isolates from France and Japan, suggesting that the vaccine could be used worldwide. A single dose of this DNA vaccine induced protection in fish at a lower dose than is usually reported in mammalian DNA vaccine studies.
Fulminant Epstein-Barr virus - infectious mononucleosis in an adult with liver failure, splenic rupture, and spontaneous esophageal bleeding with ensuing esophageal necrosis: a case report
Introduction Infectious mononucleosis is a clinical syndrome most commonly associated with primary Epstein-Barr virus infection. The majority of patients with infectious mononucleosis recovers without apparent sequelae. However, infectious mononucleosis may be associated with several acute complications. In this report we present a rare case of esophageal rupture that has never been described in the literature before. Case presentation We present the case of an 18-year-old Caucasian man affected by severe infectious mononucleosis complicated by fulminant hepatic failure, splenic rupture and esophageal necrosis. Conclusions Although primary Epstein-Barr virus infection is rarely fatal, fulminant infection may occur - in this case leading to hepatic failure, splenic rupture and esophageal necrosis, subsequently making several surgical interventions necessary. We show here that infectious mononucleosis is not only a strictly medical condition, but can also lead to severe surgical complications. PMID:24499457
Post-transplant lymphoproliferative disorder after kidney transplantation: time to adopt monitoring of Epstein-Barr virus?
Biller, P; Michaux, L; Pauw, L De; Camboni, A; Mourad, M; Kanaan, N
Although post-transplant lymphoproliferative disorder is a classical complication encountered after kidney transplantation, its diagnosis can still be challenging and its outcome life-threatening. Most cases are related to Epstein-Barr virus (EBV) infection and occur mainly in the first year post-transplant, favoured by the seronegative EBV status of the recipient transplanted with a kidney from a seropositive donor, and strong immunosuppression. We report the case of a young kidney-pancreas transplant recipient who developed post-transplant lymphoproliferative disorder (PTLD) early after transplantation, with a rapid fatal issue. We review the pathogenesis, clinical presentation, and management of PTLD with a focus on prevention. PMID:25541210
Transcriptional profiling of MHC class I genes in rainbow trout infected with infectious hematopoietic necrosis virus
Landis, E.D.; Purcell, M.K.; Thorgaard, G.H.; Wheeler, P.A.; Hansen, J.D.
Major histocompatibility complex (MHC) molecules are important mediators of cell-mediated immunity in vertebrates. MHC class IA molecules are important for host anti-viral immunity as they present intracellular antigens and regulate natural killer cell (NK) activity. MHC class Ib molecules on the other hand are less understood and have demonstrated diverse immune and non-immune functions in mammals. Rainbow trout possess a single classical MHC IA locus (Onmy-UBA) that is believed to function similar to that of mammalian MHC class Ia. Numerous MHC class Ib genes with undetermined functions have also been described in trout. Here we utilize quantitative reverse transcriptase PCR (qRT-PCR) techniques to survey the levels of basal and inducible transcription for selected trout MHC class Ib genes, sIgM and sentinels of IFN induction in response to viral infection. Basal transcription of all the class Ib genes examined in this study was lower than Onmy-UBA in nai??ve fish. UBA, along with all of the non-classical genes were induced in fish infected with virus but not in control fish. Our results support a non-classical designation for the majority of the class IB genes surveyed in this study based upon expression levels while also indicating that they may play an important role in anti-viral immunity in trout.
trans activation of the tumor necrosis factor alpha promoter by the human T-cell leukemia virus type I Tax1 protein.
Albrecht, H; Shakhov, A N; Jongeneel, C V
In a cotransfection assay, the human T-cell leukemia virus type I Tax1 gene product specifically activated transcription from the mouse tumor necrosis factor alpha promoter. The activation patterns of 5' deletion mutants, artificial enhancer constructs, and point mutations in the promoter indicate that the major Tax1-responsive element is a site at position -655 which binds the NF-kappa B/rel and NF-GMa transcription factors. Images PMID:1527856
A Systematic Approach towards Optimizing a Cohabitation Challenge Model for Infectious Pancreatic Necrosis Virus in Atlantic Salmon (Salmo salar L.).
Munang'andu, Hetron Mweemba; Santi, Nina; Fredriksen, Børge Nilsen; Løkling, Knut-Egil; Evensen, Øystein
A cohabitation challenge model was developed for use in evaluating the efficacy of vaccines developed against infectious pancreatic necrosis virus (IPNV) in Atlantic salmon (Salmo salar L) using a stepwise approach. The study involved identifying a set of input variables that were optimized before inclusion in the model. Input variables identified included the highly virulent Norwegian Sp strain NVI015-TA encoding the T217A221 motif having the ability to cause >90% mortality and a hazard risk ratio of 490.18 (p<0.000) for use as challenge virus. The challenge dose was estimated at 1x10(7) TCID50/mL per fish while the proportion of virus shedders was estimated at 12.5% of the total number of fish per tank. The model was designed based on a three parallel tank system in which the Cox hazard proportional regression model was used to estimate the minimum number of fish required to show significant differences between the vaccinated and control fish in each tank. All input variables were optimized to generate mortality >75% in the unvaccinated fish in order to attain a high discriminatory capacity (DC) between the vaccinated and control fish as a measure of vaccine efficacy. The model shows the importance of using highly susceptible fish to IPNV in the optimization of challenge models by showing that highly susceptible fish had a better DC of differentiating vaccine protected fish from the unvaccinated control fish than the less susceptible fish. Once all input variables were optimized, the model was tested for its reproducibility by generating similar results from three independent cohabitation challenge trials using the same input variables. Overall, data presented here show that the cohabitation challenge model developed in this study is reproducible and that it can reliably be used to evaluate the efficacy of vaccines developed against IPNV in Atlantic salmon. We envision that the approach used here will open new avenues for developing optimal challenge models for
A Systematic Approach towards Optimizing a Cohabitation Challenge Model for Infectious Pancreatic Necrosis Virus in Atlantic Salmon (Salmo salar L.)
Munang'andu, Hetron Mweemba; Santi, Nina; Fredriksen, Børge Nilsen; Løkling, Knut-Egil; Evensen, Øystein
A cohabitation challenge model was developed for use in evaluating the efficacy of vaccines developed against infectious pancreatic necrosis virus (IPNV) in Atlantic salmon (Salmo salar L) using a stepwise approach. The study involved identifying a set of input variables that were optimized before inclusion in the model. Input variables identified included the highly virulent Norwegian Sp strain NVI015-TA encoding the T217A221 motif having the ability to cause >90% mortality and a hazard risk ratio of 490.18 (p<0.000) for use as challenge virus. The challenge dose was estimated at 1x107 TCID50/mL per fish while the proportion of virus shedders was estimated at 12.5% of the total number of fish per tank. The model was designed based on a three parallel tank system in which the Cox hazard proportional regression model was used to estimate the minimum number of fish required to show significant differences between the vaccinated and control fish in each tank. All input variables were optimized to generate mortality >75% in the unvaccinated fish in order to attain a high discriminatory capacity (DC) between the vaccinated and control fish as a measure of vaccine efficacy. The model shows the importance of using highly susceptible fish to IPNV in the optimization of challenge models by showing that highly susceptible fish had a better DC of differentiating vaccine protected fish from the unvaccinated control fish than the less susceptible fish. Once all input variables were optimized, the model was tested for its reproducibility by generating similar results from three independent cohabitation challenge trials using the same input variables. Overall, data presented here show that the cohabitation challenge model developed in this study is reproducible and that it can reliably be used to evaluate the efficacy of vaccines developed against IPNV in Atlantic salmon. We envision that the approach used here will open new avenues for developing optimal challenge models for use
Detection of goldfish haematopoietic necrosis herpes virus (Cyprinid herpesvirus-2) with multi-drug resistant Aeromonas hydrophila infection in goldfish: First evidence of any viral disease outbreak in ornamental freshwater aquaculture farms in India.
Sahoo, P K; Swaminathan, T Raja; Abraham, Thangapalam Jawahar; Kumar, Raj; Pattanayak, S; Mohapatra, A; Rath, S S; Patra, Avijit; Adikesavalu, Harresh; Sood, Neeraj; Pradhan, P K; Das, B K; Jayasankar, P; Jena, J K
This outbreak report details of a mortality event where Cyprinid herpes virus-2 (CyHV-2) was detected in association with multidrug-resistant Aeromonas hydrophila infection in goldfish, Carassius auratus, from commercial farms. The goldfish exhibited large scale haemorrhages on the body, fins and gills, lepidorthosis, necrosed gills, protruded anus and shrunken eyes. White nodular necrotic foci in spleen and kidneys were noticed, along with necrosis and fusion of gill lamellae. Transmission electron microscopy of affected tissues revealed the presence of mature virus particles. Involvement of CyHV-2 was confirmed by PCR, sequencing and observed cytopathic effect in koi carp fin cell line along with experimental infection study. A bacterium isolated from the internal organs of affected fish was found to be pathogenic Aeromonas hydrophila having resistance to more than 10 classes of antibiotics. We postulate that CyHV-2 was the primary etiological agent responsible for this outbreak with secondary infection by A. hydrophila. The experimental infection trials in Labeo rohita and koi carp by intraperitoneal challenge with CyHV-2 tissue homogenates failed to reproduce the disease in those co-cultured fish species. This is the first report of a viral disease outbreak in organised earthen ornamental fish farms in India and bears further investigation. PMID:27172876
Hepatitis C Virus Infection and Kidney Disease: A Meta-Analysis
Martin, Paul; Dixit, Vivek; Messa, Piergiorgio
Summary Background and objectives Hepatitis C virus (HCV) infection and kidney disease are both highly prevalent diseases. The association between HCV and GN has been supported by previous research but little is known about the relationship between HCV and kidney disease. Design, setting, participants, & measurements A systematic review of the published medical literature was conducted to determine if HCV is associated with increased likelihood of kidney disease in the general population. A random-effects model was used to generate a summary estimate of the relative risk for kidney disease, defined as an estimated GFR <60 ml/min per 1.73 m2 or proteinuria, with HCV across the published studies. Results Nine clinical studies (817,917 unique individuals) were identified. Pooling of study results demonstrated the absence of a relationship between HCV seropositive status and reduced estimated GFR (adjusted relative risk, 1.12; 95% confidence interval, 0.91, 1.38; P=0.28) according to the random-effects model. HCV seropositive serology was an independent and significant risk factor for proteinuria (defined by urine dipstick test or spot urine albumin/creatinine ratio) in the general population, with a summary estimate for adjusted relative risk of 1.47 (95% confidence interval, 1.12, 1.94; P=0.006). Significant heterogeneity was observed between studies (Ri=0.82; P value by Q test, <0.001). Conclusions This meta-analysis shows that HCV is independently associated with proteinuria but not with reduced GFR in the general population. Substantial heterogeneity occurred. PMID:22403269
Early viral replication and induced or constitutive immunity in rainbow trout families with differential resistance to Infectious hematopoietic necrosis virus (IHNV)
Purcell, M.K.; LaPatra, S.E.; Woodson, J.C.; Kurath, G.; Winton, J.R.
The main objective of this study was to assess correlates of innate resistance in rainbow trout full-sibling families that differ in susceptibility to Infectious hematopoietic necrosis virus (IHNV). As part of a commercial breeding program, full-sibling families were challenged with IHNV by waterborne exposure at the 1 g size to determine susceptibility to IHNV. Progeny from select families (N = 7 families) that varied in susceptibility (ranging from 32 to 90% cumulative percent mortality (CPM)) were challenged again at the 10 g size by intra-peritoneal injection and overall mortality, early viral replication and immune responses were evaluated. Mortality challenges included 20–40 fish per family while viral replication and immune response studies included 6 fish per family at each time point (24, 48 and 72 h post-infection (hpi)). CPM at the 1 g size was significantly correlated with CPM at the 10 g size, indicating that inherent resistance was a stable trait irrespective of size. In the larger fish, viral load was measured by quantitative reverse-transcriptase PCR in the anterior kidney and was a significant predictor of family disease outcome at 48 hpi. Type I interferon (IFN) transcript levels were significantly correlated with an individual's viral load at 48 and 72 hpi, while type II IFN gene expression was significantly correlated with an individual's viral load at 24 and 48 hpi. Mean family type I but not type II IFN gene expression was weakly associated with susceptibility at 72 hpi. There was no association between mean family susceptibility and the constitutive expression of a range of innate immune genes (e.g. type I and II IFN pathway genes, cytokine and viral recognition receptor genes). The majority of survivors from the challenge had detectable serum neutralizing antibody titers but no trend was observed among families. This result suggests that even the most resistant families experienced sufficient levels of viral replication to trigger specific
Completion of the Entire Hepatitis C Virus Life Cycle in Vero Cells Derived from Monkey Kidney
Murayama, Asako; Sugiyama, Nao; Wakita, Takaji
ABSTRACT A hepatitis C virus (HCV) cell culture system incorporating the JFH-1 strain and the human hepatoma cell line HuH-7 enabled the production of infectious HCV particles. Several host factors were identified as essential for HCV replication. Supplementation of these factors in nonhepatic human cell lines enabled HCV replication and particle production. Vero cells established from monkey kidney are commonly used for the production of vaccines against a variety of viruses. In this study, we aimed to establish a novel Vero cell line to reconstruct the HCV life cycle. Unmodified Vero cells did not allow HCV infection or replication. The expression of microRNA 122 (miR-122), an essential factor for HCV replication, is notably low in Vero cells. Therefore, we supplemented Vero cells with miR-122 and found that HCV replication was enhanced. However, Vero cells that expressed miR-122 still did not allow HCV infection. We supplemented HCV receptor molecules and found that scavenger receptor class B type I (SRBI) was essential for HCV infection in Vero cells. The supplementation of apolipoprotein E (ApoE), a host factor important for virus production, enabled the production of infectious virus in Vero cells. Finally, we created a Vero cell line that expressed the essential factors miR-122, SRBI, and ApoE; the entire HCV life cycle, including infection, replication, and infectious virus production, was completed in these cells. In conclusion, we demonstrated that miR-122, SRBI, and ApoE were necessary and sufficient for the completion of the entire HCV life cycle in nonhuman, nonhepatic Vero cells. PMID:27302754
Enhancement by tumor necrosis factor alpha of dengue virus-induced endothelial cell production of reactive nitrogen and oxygen species is key to hemorrhage development.
Yen, Yu-Ting; Chen, Hsuen-Chin; Chen, Hseun-Chin; Lin, Yang-Ding; Shieh, Chi-Chang; Wu-Hsieh, Betty A
Hemorrhage is a severe manifestation of dengue disease. Virus strain and host immune response have been implicated as the risk factors for hemorrhage development. To delineate the complex interplay between the virus and the host, we established a dengue hemorrhage model in immune-competent mice. Mice inoculated intradermally with dengue virus develop hemorrhage within 3 days. In the present study, we showed by the presence of NS1 antigen and viral nuclei acid that dengue virus actively infects the endothelium at 12 h and 24 h after inoculation. Temporal studies showed that beginning at day 2, there was macrophage infiltration into the vicinity of the endothelium, increased tumor necrosis factor alpha (TNF-alpha) production, and endothelial cell apoptosis in the tissues. In the meantime, endothelial cells in the hemorrhage tissues expressed inducible nitric oxide synthase (iNOS) and nitrotyrosine. In vitro studies showed that primary mouse and human endothelial cells were productively infected by dengue virus. Infection by dengue virus induced endothelial cell production of reactive nitrogen and oxygen species and apoptotic cell death, which was greatly enhanced by TNF-alpha. N(G)-nitro-L-arginine methyl ester and N-acetyl cysteine reversed the effects of dengue virus and TNF-alpha on endothelial cells. Importantly, hemorrhage development and the severity of hemorrhage were greatly reduced in mice lacking iNOS or p47(phox) or treatment with oxidase inhibitor, pointing to the critical roles of reactive nitrogen and oxygen species in dengue hemorrhage. PMID:18842737
Antibody levels against BK virus and prostate, kidney and bladder cancers in the EPIC-Oxford cohort
Newton, R; Ribeiro, T; Casabonne, D; Alvarez, E; Touzé, A; Key, T; Coursaget, P
In a case–control study nested within the EPIC-Oxford cohort, there were no statistically significant differences in the prevalence or titre of antibodies against BK virus measured in plasma taken prior to diagnosis between cases with cancer of the prostate (n=31), kidney (n=5) or bladder (n=9) and controls (n=45). PMID:16304559
Bioinformatic characterization and gene expression pattern of apoptosis inhibitor from Macrobrachium rosenbergii challenged with infectious hypodermal and hematopoietic necrosis virus.
Arockiaraj, Jesu; Vanaraja, Puganeshwaran; Easwvaran, Sarasvathi; Singh, Arun; Othman, Rofina Yasmin; Bhassu, Subha
Apoptosis is genetically programmed cellular killing processes that execute unnecessary or infected cells. It plays an important role in embryogenesis, homeostasis, insect metamorphosis and immunity. Apoptosis inhibitor (MrIAP) was sequenced from the freshwater giant prawn Macrobrachium rosenbergii using Illumina Solexa Genome Analyzer Technique. MrIAP consisted of 1753 base pair nucleotides encoded 535 polypeptide with an estimated molecular mass of 60 kDa. MrIAP amino acid sequence contains IAP superfamily domain between 5 and 490. The deduced amino acid sequences of the MrIAP were aligned with the other IAP family members. The highest sequence similarity was observed in IAP-5 from ant Camponotus floridanus (67%) followed by IAP from body louse Pediculus humanus corporis (66%) and the lowest (62%) in IAP-5 isoform-5 from common chimpanzee Pan troglodytes and IAP-5 from Aedes aegypti. The IAP phylogenetic tree showed that MrIAP closely related to other arthropod blacklegged tick Ixodes scapularis, formed a sister group with IAP from a hemichordate acorn worm Saccoglossus kowalevskii and finally clustered together with IAPs from fish groups. The quantitative real time PCR analysis revealed that significantly (P < 0.05) highest expression was noticed in hepatopancreas and significantly (P < 0.05) lowest expression in pleopods. Based on the results of gene expression analysis, MrIAP mRNA transcription in M. rosenbergii challenged to infectious hypodermal and hematopoietic necrosis virus (IHHNV) was highly induced in hepatopancreas. The collective results of this study indicate that the MrIAP is an essential immune gene and influences the immune response against IHHNV infection in M. rosenbergii. PMID:21945707
Prediction model for sequence variation in the glycoprotein gene of infectious hematopoietic necrosis virus in California, U.S.A.
Kelley, Garry O; Garabed, Rebecca; Branscum, Adam; Perez, Andres; Thurmond, Mark
The influence of spatio-temporal factors on genetic variation of infectious hematopoietic necrosis virus (IHNV) is an active area of research. Using host-isolate pairs collected from 1966 to 2004 for 237 IHNV isolates from California and southern Oregon, we examined genetic variation of the mid-G gene of IHNV that could be quantified across times and geographic locations. Information hypothesized to influence genetic variation was environmental and/or fish host demographic factors, viz. location (inland or coastal), year of isolation, habitat (river, lake, or hatchery), the agent factors of subgroup (LI or LII) and serotype (1, 2, or 3), and the host factors of fish age (juvenile or adult), sex (male or female), and season of spawning run (spring, fall, late fall, winter). Inverse distance weighting (IDW) was performed to create isopleth maps of the genetic distances of each subgroup. IDW maps showed that more genetic divergence was predicted for isolates found inland (for both subgroups: LI and LII) than for coastal watershed isolates. A mixed-effect beta regression with a logit link function was used to seek associations between genetic distances and hypothesized explanatory factors. The model that best described genetic distance contained the factors of location, year of isolation, and the interaction between location and year. Our model suggests that genetic distance was greater for isolates collected from 1966 to 2004 at inland locations than for isolates found in coastal watersheds during the same years. The agreement between the IDW and beta regression analyses quantitatively supports our conclusion that, during this time period, more genetic variation existed within subgroup LII in inland watersheds than within coastal LI isolates. PMID:18286806
A nuclear localization of the infectious haematopoietic necrosis virus NV protein is necessary for optimal viral growth
Choi, M.K.; Moon, C.H.; Ko, M.S.; Lee, U.-H.; Cho, W.J.; Cha, S.J.; Do, J.W.; Heo, G.J.; Jeong, S.G.; Hahm, Y.S.; Harmache, A.; Bremont, M.; Kurath, G.; Park, J.-W.
The nonvirion (NV) protein of infectious hematopoietic necrosis virus (IHNV) has been previously reported to be essential for efficient growth and pathogenicity of IHNV. However, little is known about the mechanism by which the NV supports the viral growth. In this study, cellular localization of NV and its role in IHNV growth in host cells was investigated. Through transient transfection in RTG-2 cells of NV fused to green fluorescent protein (GFP), a nuclear localization of NV was demonstrated. Deletion analyses showed that the 32EGDL35 residues were essential for nuclear localization of NV protein, and fusion of these 4 amino acids to GFP directed its transport to the nucleus. We generated a recombinant IHNV, rIHNV-NV-ΔEGDL in which the 32EGDL35 was deleted from the NV. rIHNVs with wild-type NV (rIHNV-NV) or with the NV gene replaced with GFP (rIHNV-ΔNV-GFP) were used as controls. RTG-2 cells infected with rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL yielded 12- and 5-fold less infectious virion, respectively, than wild type rIHNV-infected cells at 48 h post-infection (p.i.). While treatment with poly I:C at 24 h p.i. did not inhibit replication of wild-type rIHNVs, replication rates of rIHNV-ΔNV-GFP and rIHNV-NV-ΔEGDL were inhibited by poly I:C. In addition, both rIHNV-ΔNV and rIHNV-NV-ΔEGDL induced higher levels of expressions of both IFN1 and Mx1 than wild-type rIHNV. These data suggest that the IHNV NV may support the growth of IHNV through inhibition of the INF system and the amino acid residues of 32EGDL35 responsible for nuclear localization are important for the inhibitory activity of NV.
Apoptosis induced by tumor necrosis factor-alpha in rat hepatocyte cell lines expressing hepatitis B virus.
Guilhot, S.; Miller, T.; Cornman, G.; Isom, H. C.
Three well differentiated SV40-immortalized rat hepatocyte cell lines, CWSV1, CWSV2, and CWSV14, and Hepatitis B Virus (HBV)-producing cell lines derived from them were examined for sensitivity to tumor necrosis factor (TNF)-alpha. CWSV1, CWSV2, and CWSV14 cells were co-transfected with a DNA construct containing a dimer of the HBV genome and the neo gene and selected in G418 to generate stable cell lines. Characterization of these cell lines indicated that they contain integrated HBV DNA, contain low molecular weight HBV DNA compatible with the presence of HBV replication intermediates, express HBV transcripts, and produce HBV proteins. The viability of CWSV1, CWSV2, and CWSV2 cells was not significantly altered when they were treated with TNF-alpha at concentrations as high as 20,000 U/ml. The HBV-expressing CWSV1 cell line, SV1di36, and the HBV-expressing CWSV14 cell line, SV14di208, were also not killed when treated with TNF-alpha. However, the HBV-expressing CWSV2 cell line, SV2di366, was extensively killed when treated with TNF-alpha at concentrations ranging from 200 to 20,000 U/ml. Analysis of several different HBV-producing CWSV2 cell lines indicated that TNF-alpha killing depended upon the level of HBV expression. The TNF-alpha-induced cell killing in high HBV-producing CWSV2 cell lines was accompanied by the presence of an oligonucleosomal DNA ladder characteristic of apoptosis. Images Figure 2 Figure 3 Figure 4 Figure 6 Figure 9 Figure 10 Figure 11 PMID:8774135
Sequence-Specific, RNA–Protein Interactions Overcome Electrostatic Barriers Preventing Assembly of Satellite Tobacco Necrosis Virus Coat Protein
Ford, Robert J.; Barker, Amy M.; Bakker, Saskia E.; Coutts, Robert H.; Ranson, Neil A.; Phillips, Simon E.V.; Pearson, Arwen R.; Stockley, Peter G.
We have examined the roles of RNA–coat protein (CP) interactions in the assembly of satellite tobacco necrosis virus (STNV). The viral genomic RNA encodes only the CP, which comprises a β-barrel domain connected to a positively charged N-terminal extension. In the previous crystal structures of this system, the first 11 residues of the protein are disordered. Using variants of an RNA aptamer sequence isolated against the CP, B3, we have studied the sequence specificity of RNA-induced assembly. B3 consists of a stem–loop presenting the tetra-loop sequence ACAA. There is a clear preference for RNAs encompassing this loop sequence, as measured by the yield of T = 1 capsids, which is indifferent to sequences within the stem. The B3-containing virus-like particle has been crystallised and its structure was determined to 2.3 Å. A lower-resolution map encompassing density for the RNA has also been calculated. The presence of B3 results in increased ordering of the N-terminal helices located at the particle 3-fold axes, which extend by roughly one and a half turns to encompass residues 8–11, including R8 and K9. Under assembly conditions, STNV CP in the absence of RNA is monomeric and does not self-assemble. These facts suggest that a plausible model for assembly initiation is the specific RNA-induced stabilisation of a trimeric capsomere. The basic nature of the helical extension suggests that electrostatic repulsion between CPs prevents assembly in the absence of RNA and that this barrier is overcome by correct placement of appropriately orientated helical RNA stems. Such a mechanism would be consistent with the data shown here for assembly with longer RNA fragments, including an STNV genome. The results are discussed in light of a first stage of assembly involving compaction of the genomic RNA driven by multiple RNA packaging signal–CP interactions. PMID:23318955
Purification, crystallization and preliminary X-ray analysis of truncated and mutant forms of VP4 protease from infectious pancreatic necrosis virus
Lee, Jaeyong; Feldman, Anat R.; Chiu, Elaine; Chan, Charlena; Kim, You-Na; Delmas, Bernard; Paetzel, Mark
Various truncated and mutant forms of the protease VP4 from infectious pancreatic necrosis virus were used to generate two different crystal forms of VP4 which diffracted to beyond 2.4 Å resolution. In viruses belonging to the Birnaviridae family, virus protein 4 (VP4) is the viral protease responsible for the proteolytic maturation of the polyprotein encoding the major capsid proteins (VP2 and VP3). Infectious pancreatic necrosis virus (IPNV), the prototype of the aquabirnavirus genus, is the causative agent of a contagious disease in fish which has a large economic impact on aquaculture. IPNV VP4 is a 226-residue (24.0 kDa) serine protease that utilizes a Ser/Lys catalytic dyad mechanism (Ser633 and Lys674). Several truncated and mutant forms of VP4 were expressed in a recombinant expression system, purified and screened for crystallization. Two different crystal forms diffract beyond 2.4 Å resolution. A triclinic crystal derived from one mutant construct has unit-cell parameters a = 41.7, b = 69.6, c = 191.6 Å, α = 93.0, β = 95.1, γ = 97.7°. A hexagonal crystal with space group P6{sub 1}22/P6{sub 5}22 derived from another mutant construct has unit-cell parameters a = 77.4, b = 77.4, c = 136.9 Å.
A nuclear localization signal in the matrix of spleen necrosis virus (SNV) does not allow efficient gene transfer into quiescent cells with SNV-derived vectors
Caron, Marie-Christine; Caruso, Manuel . E-mail: firstname.lastname@example.com
A major limitation in gene therapy for vectors derived from Moloney murine leukemia virus (MLV) is that they only deliver genes into dividing cells. In this study, a careful comparison of spleen necrosis virus (SNV)-derived vectors with MLV and human immunodeficiency virus (HIV)-1 retroviral vectors indicated that SNV vectors can deliver genes 4-fold more efficiently than MLV vectors into aphidicolin-arrested cells, although at a 25-fold lower efficiency than HIV-1-derived vectors. Furthermore, the addition of a NLS in the SNV matrix (MA) that mimics the one located in HIV-1 MA did not increase the ability of SNV vectors to transfer genes into arrested cells. Also, we found that the RD114 envelope was able to pseudotype SNV viral particles in a very efficient manner.
In vivo fitness correlates with host-specific virulence of Infectious hematopoietic necrosis virus (IHNV) in sockeye salmon and rainbow trout
Penaranda, M.M.D.; Wargo, A.R.; Kurath, G.
The relationship between virulence and overall within-host fitness of the fish rhabdovirus Infectious hematopoietic necrosis virus (IHNV) was empirically investigated in vivo for two virus isolates belonging to different IHNV genogroups that exhibit opposing host-specific virulence. U group isolates are more virulent in sockeye salmon and M group isolates are more virulent in rainbow trout. In both single and mixed infections in the two fish hosts, the more virulent IHNV type exhibited higher prevalence and higher viral load than the less virulent type. Thus, a positive correlation was observed between higher in vivo fitness and higher host-specific virulence in sockeye salmon and rainbow trout. Comparisons of mean viral loads in single and mixed infections revealed no evidence for limitation due to competition effects between U and M viruses in either rainbow trout or sockeye salmon co-infections.
Dialysis-requiring acute kidney injury among hospitalized adults with documented hepatitis C Virus infection: a nationwide inpatient sample analysis.
Nadkarni, G N; Patel, A; Simoes, P K; Yacoub, R; Annapureddy, N; Kamat, S; Konstantinidis, I; Perumalswami, P; Branch, A; Coca, S G; Wyatt, C M
Chronic hepatitis C virus (HCV) infection may cause kidney injury, particularly in the setting of cryoglobulinemia or cirrhosis; however, few studies have evaluated the epidemiology of acute kidney injury in patients with HCV. We aimed to describe national temporal trends of incidence and impact of severe acute kidney injury (AKI) requiring renal replacement 'dialysis-requiring AKI' in hospitalized adults with HCV. We extracted our study cohort from the Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project using data from 2004 to 2012. We defined HCV and dialysis-requiring acute kidney injury based on previously validated ICD-9-CM codes. We analysed temporal changes in the proportion of hospitalizations complicated by dialysis-requiring AKI and utilized survey multivariable logistic regression models to estimate its impact on in-hospital mortality. We identified a total of 4,603,718 adult hospitalizations with an associated diagnosis of HCV from 2004 to 2012, of which 51,434 (1.12%) were complicated by dialysis-requiring acute kidney injury. The proportion of hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly from 0.86% in 2004 to 1.28% in 2012. In-hospital mortality was significantly higher in hospitalizations complicated by dialysis-requiring acute kidney injury vs those without (27.38% vs 2.95%; adjusted odds ratio: 2.09; 95% confidence interval: 1.74-2.51). The proportion of HCV hospitalizations complicated by dialysis-requiring acute kidney injury increased significantly between 2004 and 2012. Similar to observations in the general population, dialysis-requiring acute kidney injury was associated with a twofold increase in odds of in-hospital mortality in adults with HCV. These results highlight the burden of acute kidney injury in hospitalized adults with HCV infection. PMID:26189719
African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era.
Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi
Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era. PMID:25949944
African origins and chronic kidney disease susceptibility in the human immunodeficiency virus era
Kasembeli, Alex N; Duarte, Raquel; Ramsay, Michèle; Naicker, Saraladevi
Chronic kidney disease (CKD) is a major public health problem worldwide with the estimated incidence growing by approximately 6% annually. There are striking ethnic differences in the prevalence of CKD such that, in the United States, African Americans have the highest prevalence of CKD, four times the incidence of end stage renal disease when compared to Americans of European ancestry suggestive of genetic predisposition. Diabetes mellitus, hypertension and human immunodeficiency virus (HIV) infection are the major causes of CKD. HIV-associated nephropathy (HIVAN) is an irreversible form of CKD with considerable morbidity and mortality and is present predominantly in people of African ancestry. The APOL1 G1 and G2 alleles were more strongly associated with the risk for CKD than the previously examined MYH9 E1 risk haplotype in individuals of African ancestry. A strong association was reported in HIVAN, suggesting that 50% of African Americans with two APOL1 risk alleles, if untreated, would develop HIVAN. However these two variants are not enough to cause disease. The prevailing belief is that modifying factors or second hits (including genetic hits) underlie the pathogenesis of kidney disease. This work reviews the history of genetic susceptibility of CKD and outlines current theories regarding the role for APOL1 in CKD in the HIV era. PMID:25949944
Occurrence and management of hepatitis B virus reactivation following kidney transplantation.
Grotz, W; Rasenack, J; Benzing, T; Berthold, H; Peters, T; Walter, E; Schollmeyer, P; Rump, L C
A 28-year-old woman was kidney transplanted. She had an inapparent hepatitis B virus (HBV) infection 2 years previously. At the time of transplantation she was hepatitis B surface antigen (HBsAg) negative, anti-HBs, anti-HBc, anti-HBe and anti-HCV antibody positive and her transaminase activities were within the normal range. The donor of the kidney allograft was HBV negative. Twelve weeks after transplantation a life-threatening liver failure occurred with a rapid rise of alanine aminotransferase (ALT) to 1427 U/l and a decrease of the prothrombin time to 25% of normal value. Anti-HBs had become negative, anti-HBc and anti-HBe titers had decreased. HBsAg became positive, associated with a HBV DNA of 3 x 10(8) genome equivalents/ml. Azathioprine and prednisone were withdrawn and foscarnet therapy was started. This therapy led to a decrease of ALT activity associated with an elimination of HBsAg and HBV DNA. Eight months after transplantation liver function tests were within the normal range. Graft rejection did not occur despite low or intermittent cessation of immunosuppressive therapy. PMID:9696436
Systematic Serological Testing for Hepatitis E Virus in Kidney Transplant Recipients
Legris, Tristan; Motte, Anne; Vacher-Coponat, Henri; Fages, Lucie; Jourde-Chiche, Noémie; Borentain, Patrick; Jaubert, Dominique; Gerolami, René; Colson, Philippe
Hepatitis E virus (HEV) genotype 3 is endemic in Europe and hyperendemic in southern France. Recent reports of a high prevalence of HEV RNA in blood donations and in culinary specialties from this geographical area confirmed the endemicity of HEV and sources of viral transmission in this geographical area. HEV causes acute and chronic hepatitis in solid organ transplant recipients. Since March 2012, we have implemented systematic HEV serological testing in our cohort of kidney transplant recipients (KTRs) in Marseille in southeastern France. The aim of our study was to assess HEV exposure in this cohort between March 2012 and May 2014. During these 27 months, we found that 39% of the patients who underwent kidney transplantation had an anti-HEV IgG response using a sensitive microplate enzyme immunoassay. This seroprevalence was approximately 43% at both 1 and 8 years after, using the same assay. In addition, systematic HEV serological testing detected 6 cases of HEV infection among 578 KTRs (1%) during the 27 months of the study, with 5 at an acute stage and 1 at a chronic stage. In conclusion, continuous HEV monitoring in this population is useful for better understanding the epidemiology of HEV in France, because these patients are a well-monitored population. Moreover, HEV monitoring in KTRs is clinically relevant because HEV represents a clinical threat in these patients. Nevertheless, HEV serological testing may be more fruitful for identifying HEV infections when performed in cases of biological liver abnormalities than when performed systematically. PMID:25694530
Serum creatinine elevation after switch to dolutegravir in a human immunodeficiency virus-positive kidney transplant recipient.
Lee, D H; Malat, G E; Bias, T E; Harhay, M N; Ranganna, K; Doyle, A M
Dolutegravir is a preferred antiretroviral drug for human immunodeficiency virus (HIV)-infected patients following solid organ transplantation. It has potent antiretroviral activity and does not interact with calcineurin inhibitors. We describe a case of an HIV-infected kidney transplant patient, who was noted to have a rising serum creatinine following initiation of dolutegravir. At first, an acute rejection episode was suspected, but this finding was later attributed to inhibition of creatinine secretion by dolutegravir. We suggest that an awareness of this potential effect of dolutegravir is important for providers who take care of HIV-positive kidney transplant recipients, in order to prevent potentially unnecessary testing. PMID:27159656
Detecting molecular adaptation at individual codons in the glycoprotein gene of the geographically diversified infectious hematopoietic necrosis virus, a fish rhabdovirus.
Padhi, Abinash; Verghese, Bindhu
Salmonid fishes, the principal hosts of the infectious hematopoietic necrosis virus (IHNV), are a candidate species for aquaculture in many countries. IHNV causes an acute disease resulting in severe economic loss in salmonid fish farming. Previous phylogenetic analyses revealed the existence of multiple genogroups of this virus throughout the geographical range of its host. Here, we report the importance of natural selection in shaping the evolution of certain codons at the surface glycoprotein (G-protein) gene of this virus. Maximum likelihood (ML)-based codon substitution analyses revealed that approximately 2.8% of the codons for the entire G-protein are shown to have higher nonsynonymous substitution per nonsynonymous site (dn) than the synonymous substitutions per synonymous site (ds) (dn/ds=omega>4.335). Thus, the data suggest that positive selection (omega>1) is the major driving force in the evolution of certain codons. However, majority of these positively selected sites cannot be mapped to the regions of antigenic determinants of IHNV. Based on the reports of previous studies, epitopes with positively selected sites are immunodominant and viruses can escape from immune responses by producing antigenic variation at positively selected sites, therefore, vaccines directed against these neutralizing epitopes of IHNV that consist of no positively selected sites will be more effective. Some of the positively selected sites showed radical change in amino acids with respect to their charge and polarity; however, it is unclear how these changes affect the fitness of the virus. PMID:18178282
Development of reverse transcription loop-mediated isothermal amplification assay as a simple detection method of Chrysanthemum stem necrosis virus in chrysanthemum and tomato.
Suzuki, Ryoji; Fukuta, Shiro; Matsumoto, Yuho; Hasegawa, Toru; Kojima, Hiroko; Hotta, Makiko; Miyake, Noriyuki
For a simple and rapid detection of Chrysanthemum stem necrosis virus (CSNV) from chrysanthemum and tomato, a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed. A primer set designed to the genome sequences of CSNV worked most efficiently at 63°C and could detect CSNV RNA within 12min by fluorescence monitoring using an isothermal DNA amplification and fluorescence detection device. The result of a specificity test using seven other viruses and one viroid-infectable chrysanthemum or tomato showed that the assay could amplify CSNV specifically, and a sensitivity comparison showed that the RT-LAMP assay was as sensitive as the reverse transcriptase polymerase chain reaction. The RT-LAMP assay using crude RNA, extracted simply, could detect CSNV. Overall, the RT-LAMP assay was found to be a simple, specific, convenient, and time-saving method for CSNV detection. PMID:27400833
Isolated limb perfusion with melphalan, tumour necrosis factor-alpha and oncolytic vaccinia virus improves tumour targeting and prolongs survival in a rat model of advanced extremity sarcoma.
Pencavel, Tim D; Wilkinson, Michelle J; Mansfield, David C; Khan, Aadil A; Seth, Rohit; Karapanagiotou, Eleni M; Roulstone, Victoria; Aguilar, Richard J; Chen, Nanhai G; Szalay, Aladar A; Hayes, Andrew J; Harrington, Kevin J
Isolated limb perfusion (ILP) is a treatment for advanced extremity sarcoma and in-transit melanoma. Advancing this procedure by investigating the addition of novel agents, such as cancer-selective oncolytic viruses, may improve both the therapeutic efficacy of ILP and the tumour-targeted delivery of oncolytic virotherapy. Standard in vitro assays were used to characterise single agent and combinatorial activities of melphalan, tumour necrosis factor-alpha (TNF-α) and Lister strain vaccinia virus (GLV-1h68) against BN175 rat sarcoma cells. An orthotopic model of advanced extremity sarcoma was used to evaluate survival of animals after ILP with combinations of TNF-α, melphalan and GLV-1h68. We investigated the efficiency of viral tumour delivery by ILP compared to intravenous therapy, the locoregional and systemic biodistribution of virus after ILP, and the effect of mode of administration on antibody response. The combination of melphalan and GLV-1h68 was synergistic in vitro. The addition of virus to standard ILP regimens was well tolerated and demonstrated superior tumour targeting compared to intravenous administration. Triple therapy (melphalan/TNF-α/GLV-1h68) resulted in increased tumour growth delay and enhanced survival compared to other treatment regimens. Live virus was recovered in large amounts from perfused regions, but in smaller amounts from systemic organs. The addition of oncolytic vaccinia virus to existing TNF-α/melphalan-based ILP strategies results in survival advantage in an immunocompetent rat model of advanced extremity sarcoma. Virus administered by ILP has superior tumour targeting compared to intravenous delivery. Further evaluation and clinical translation of this approach is warranted. PMID:24978211
Infections of nervous necrosis virus in wild and cage-reared marine fish from South China Sea with unexpected wide host ranges.
Liu, X D; Huang, J N; Weng, S P; Hu, X Q; Chen, W J; Qin, Z D; Dong, X X; Liu, X L; Zhou, Y; Asim, M; Wang, W M; He, J G; Lin, L
The concerns about the impact of the nervous necrosis virus (NNV) infections in wild fish have been raised. This paper presents the results of quarterly surveys of NNV in wild and cage-reared marine fish from South China Sea. Samples of 892 wild fish belonging to 69 species and 381 cage-reared fish belonging to 11 species were collected and were detected by seminested PCR and nested PCR. In the case of seminested PCR, the positive signal was detected in 3.0% and 3.1% samples of wild and cage-reared fish, respectively. However, by nested RT-PCR, the positive signal was observed in 42.3% and 63.0% samples of wild and cage-reared fish, respectively. If the fish species were considered, the positive signal was detected in 21.7% and 72.7% species of wild and cage-reared fish by seminested PCR assay, respectively. However, by nested RT-PCR, the positive signal was observed in 65.2% and 100% species of wild and cage-reared fish, respectively. The nucleotide sequences of the nested PCR products were determined. Phylogenetic tree showed that all the obtained viral isolates belonged to the red-spotted grouper nervous necrosis virus (RGNNV) genotype. Thirty-five species of the marine fish were the new hosts of NNV. PMID:24943478
Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense
Wang, Xing; Li, Yun; Liu, Shan; Yu, Xiaoliang; Li, Lin; Shi, Cuilin; He, Wenhui; Li, Jun; Xu, Lei; Hu, Zhilin; Yu, Lu; Yang, Zhongxu; Chen, Qin; Ge, Lin; Zhang, Zili; Zhou, Biqi; Jiang, Xuejun; Chen, She; He, Sudan
The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6–RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1–infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism. PMID:25316792
Negligible risk associated with the movement of processed rainbow trout, Oncorhynchus mykiss (Walbaum), from an infectious haematopoietic necrosis virus (IHNV) endemic area
LaPatra, S.E.; Batts, W.N.; Overturf, K.; Jones, G.N.; Shewmaker, W.D.; Winton, J.R.
To assess the risk of transmission of infectious haematopoietic necrosis virus (IHNV) associated with the movement of processed rainbow trout, Oncorhynchus mykiss, from an area where the virus is endemic, 240 freshly eviscerated fish (225-500 g) exhibiting spinal curvature or spinal compression types of deformities were tested for IHNV by virus isolation and polymerase chain reaction (PCR) techniques. Commercially produced rainbow trout, approximately 1-year-old, that exhibited spinal deformities were considered to have had a high likelihood of having survived an outbreak of IHN. Serological analysis of fish exhibiting spinal curvature or spinal compression types of deformities for anti-IHNV antibodies resulted, in 71 and 50% of the serum samples, respectively, with detectable neutralization activity suggesting previous infection with IHNV. A portion of the skin and muscle in the area of the deformity was collected, as well as brain tissue from each commercially processed fish. Tissue homogenates were tested for IHNV using the epithelioma papulosum cyprini (EPC) cell line pretreated with polyethylene glycol and the chinook salmon embryo (CHSE-214) cell line using standard methods. Nested, reverse transcriptase (RT)-PCR for the detection of IHNV used the central 1231 bp portion of the glycoprotein (G) challenge studies and is suggested as a mechanism responsible for virus clearance. These results provide scientific information that can be used to assess the risk associated with the movement of processed rainbow trout from an IHNV endemic area.
The dose-dependent effect on protection and humoral response to a DNA vaccine against Infectious Hematopoietic Necrosis (IHN) virus in subyearling rainbow trout
LaPatra, Scott E.; Corbeil, Serge; Jones, Gerald R.; Shewmaker, William D.; Kurath, Gael
A dose–response study that used the DNA vaccine pIHNw-G against infectious hematopoietic necrosis virus (IHNV) showed that complete and highly significant (P < 0.001) protection against a virus injection challenge can be attained in subyearling rainbow trout Oncorhynchus mykiss (145–160 g, 8- to 10-months-old) 6 weeks after a single intramuscular injection with doses as low as 1 μg. Complete protection was also reproducibly demonstrated at higher vaccine doses; however, no protection was observed with a 0.1-μg dose. Virus-neutralizing antibody titers were detected in fish that had been vaccinated with different doses of the DNA vaccine and then sham-infected; there appeared to be a dose-dependent effect, with higher titers obtained with higher doses of vaccine. The DNA-vaccinated animals that survived virus challenge had significantly (P < 0.05) higher neutralizing antibody titers than sham-infected, DNA-vaccinated control fish. Additionally, the titers detected in the IHN survivors exhibited a significant (P < 0.05) dose-dependent effect, with the highest titers being present in fish that received the highest vaccine doses.
The P25 Protein of Potato Virus X (PVX) Is the Main Pathogenicity Determinant Responsible for Systemic Necrosis in PVX-Associated Synergisms
Aguilar, Emmanuel; Almendral, David; Allende, Lucía; Pacheco, Remedios; Chung, Bong Nam; Canto, Tomás
ABSTRACT Most plant viruses counter the RNA silencing-based antiviral defense by expressing viral suppressors of RNA silencing (VSRs). In this sense, VSRs may be regarded as virulence effectors that can be recognized by the host as avirulence (avr) factors to induce R-mediated resistance. We made use of Agrobacterium-mediated transient coexpression of VSRs in combination with Potato virus X (PVX) to recapitulate in local tissues the systemic necrosis (SN) caused by PVX-potyvirus synergistic infections in Nicotiana benthamiana. The hypersensitive response (HR)-like response was associated with an enhanced accumulation of PVX subgenomic RNAs. We further show that expression of P25, the VSR of PVX, in the presence of VSR from different viruses elicited an HR-like response in Nicotiana spp. Furthermore, the expression of P25 by a Plum pox virus (PPV) vector was sufficient to induce an increase of PPV pathogenicity that led to necrotic mottling. A frameshift mutation in the P25 open reading frame (ORF) of PVX did not lead to necrosis when coexpressed with VSRs. These findings indicate that P25 is the main PVX determinant involved in eliciting a systemic HR-like response in PVX-associated synergisms. Moreover, we show that silencing of SGT1 and RAR1 attenuated cell death in both PVX-potyvirus synergistic infection and the HR-like response elicited by P25. Our study underscores that P25 variants that have impaired ability to suppress RNA silencing cannot act as elicitors when synergized by the presence of other VSRs. These findings highlight the importance of RNA silencing suppression activity in the HR-like response elicited by VSRs in certain hosts. IMPORTANCE The work presented here describes how the activity of the PVX suppressor P25 elicits an HR-like response in Nicotiana spp. when overexpressed with other VSR proteins. This finding suggests that the SN response caused by PVX-associated synergisms is a delayed immune response triggered by P25, once it reaches a
Limited Interference at the Early Stage of Infection between Two Recombinant Novirhabdoviruses: Viral Hemorrhagic Septicemia Virus and Infectious Hematopoietic Necrosis Virus▿ †
Biacchesi, Stéphane; Lamoureux, Annie; Mérour, Emilie; Bernard, Julie; Brémont, Michel
The genome sequence of a hypervirulent novirhabdovirus, viral hemorrhagic septicemia virus (VHSV) French strain 23-75, was determined. Compared to the genome of the prototype Fil3 strain, a number of substitutions, deletions, and insertions were observed. Following the establishment of a plasmid-based minigenome replication assay, recombinant VHSV (rVHSV) was successfully recovered. rVHSV exhibits wild-type-like growth properties in vitro as well as in vivo in rainbow trout. The dispensable role of NV for the novirhabdovirus replication was confirmed by generating rVHSV-ΔNV, in which the NV gene was deleted. This deletion mutant was shown to be as debilitated as that previously described for infectious hematopoietic necrosis virus (IHNV), a distantly related novirhabdovirus (S. Biacchesi, M. I. Thoulouze, M. Bearzotti, Y. X. Yu, and M. Bremont, J. Virol. 74:11247-11253, 2000). Recombinant VHSV and IHNV expressing tdTomato and GFPmax reporter genes, respectively, were generated, demonstrating the potential of these rhabdoviruses to serve as viral vectors. Interestingly, rIHNV-GFPmax could be recovered using the replicative complex proteins of either virus, whereas rVHSV-Tomato could be recovered only by using its own replicative complex, reflecting that the genome signal sequences of VHSV are relatively distant from those of IHNV and do not allow their cross-recognition. Moreover, the use of heterologous protein combinations underlined the importance of strong protein-protein interactions for the formation of a functional ribonucleoprotein complex. The rIHNV-GFPmax and rVHSV-Tomato viruses were used to simultaneously coinfect cell monolayers. It was observed that up to 74% of the cell monolayer was coinfected by both viruses, demonstrating that a limited interference phenomenon exists during the early stage of primary infection, and it was not mediated by a cellular antiviral protein or by some of the viral proteins. PMID:20631140
Molecular epidemiology reveals emergence of a virulent infectious hematopoietic necrosis (IHN) virus strain in wild salmon and its transmission to hatchery fish
Anderson, Eric D.; Engelking, H. Mark; Emmenegger, Eveline J.; Kurath, Gael
Infectious hematopoietic necrosis virus (IHNV) has been known to be a significant salmonid pathogen in the Pacific Northwest of North America for decades. The goal of this study was to characterize the IHNV genetic heterogeneity and viral traffic over time at a study site in the Deschutes River watershed in Oregon, with an emphasis on the epidemiology of IHNV types causing epidemics in wild kokanee Oncorhynchus nerkabetween 1991 and 1995. The study site included kokanee spawning grounds in the Metolius River and Lake Billy Chinook downstream, in which the IHNV epidemics occurred in 2- and 3-year-old kokanee, and the Round Butte Fish Hatchery at the outflow of the lake. Forty-two IHNV isolates collected from this area between 1975 and 1995 were characterized on a genetic basis by ribonuclease (RNase) protection fingerprint analyses of the virus nucleocapsid, glycoprotein, and nonvirion genes. Analysis of the 16 identified composite haplotypes suggested that both virus evolution and introduction of new IHNV strains contributed to the genetic diversity observed. The results indicated that the 1991–1995 epidemics in kokanee from Lake Billy Chinook were due to a newly introduced IHNV type that was first detected in spawning adult kokanee in 1988 and that this virus type was transmitted from the wild kokanee to hatchery fish downstream in 1991. Twelve IHNV haplotypes were found at Round Butte Fish Hatchery, indicating a series of virus displacement events during the 20-year period examined. This work shows that IHNV traffic can be much more complex than was previously recognized, and the results have implications for fisheries management at the hatchery and throughout the watershed.
Differential growth of U and M type infectious haematopoietic necrosis virus in a rainbow trout–derived cell line, RTG-2
Kurath, Gael; Purcell, Maureen K.; Wargo, Andrew; Park, Jeong Woo; Moon, Chang Hoon
Infectious haematopoietic necrosis virus (IHNV) is one of the most important viral pathogens of salmonids. In rainbow trout, IHNV isolates in the M genogroup are highly pathogenic, while U genogroup isolates are significantly less pathogenic. We show here that, at a multiplicity of infection (MOI) of 1, a representative U type strain yielded 42-fold less infectious virus than an M type strain in the rainbow trout–derived RTG-2 cell line at 24 h post-infection (p.i.). However, at an MOI of 10, there was only fivefold difference in the yield of infectious virus between the U and M strains. Quantification of extracellular viral genomic RNA suggested that the number of virus particles released from cells infected with the U strain at a MOI of 1 was 47-fold lower than from M-infected cells, but U and M virions were equally infectious by particle to infectivity ratios. At an MOI of 1, U strain intracellular viral genome accumulation and transcription were 37- and 12-fold lower, respectively, than those of the M strain at 24 h p.i. Viral nucleocapsid (N) protein accumulation in U strain infections was fivefold lower than in M strain infections. These results suggest that the block in U type strain growth in RTG-2 cells was because of the effects of reduced genome replication and transcription. The reduced growth of the U strain does not seem to be caused by defective genes, because the U and M strains grew equally well in the permissive epithelioma papulosum cyprini cell line at an MOI of 1. This suggests that host-specific factors in RTG-2 cells control the growth of the IHNV U and M strains differently, leading to growth restriction of the U type virus during the RNA synthesis step.
Susceptibility to an inoculum of infectious hypodermal and haematopoietic necrosis virus (IHHNV) in three batches of whiteleg shrimp Litopenaeus vannamei (Boone, 1931)
Escobedo-Bonilla, César Marcial; Rangel, José Luis Ibarra
Abstract The present study evaluated the susceptibility of three different batches of whiteleg shrimp Litopenaeus vannamei from Mexico to an inoculum of infectious hypodermal and haematopoietic necrosis virus (IHHNV). Each of the three shrimp batches came from a different hatchery. Because of their origin, it was possible that the genetic makeup of these batches was different among each other. The three batches tested showed differences in IHHNV susceptibility. Here, susceptibility is defined as the capacity of the host to become infected, and it can be measured by the infectivity titer. Susceptibility to IHHNV was observed in decreasing order in shrimp from batch 1 (hatchery from El Rosario, Sinaloa), batch 3 (hatchery from Nayarit) and batch 2 (hatchery from El Walamo, Sinaloa), respectively. The largest susceptibility difference between batches was 5012 times, and that between early and late juveniles from the same batch was 25 times. These results indicate that within a species, susceptibility to a pathogen such as IHHNV can have large differences. Susceptibility to pathogens is an important trait to consider before performing studies on pathogenesis. It may influence virological parameters such as speed of replication, pathogenicity and virus titer. In order to evaluate the potential use of IHHNV as a natural control agent against white spot syndrome virus (WSSV), it is necessary to know host susceptibility and the kinetics of IHHNV infection. These features can help to determine the conditions in which IHHNV could be used as antagonist in a WSSV infection. PMID:25561847
Tumor necrosis factor alpha is reparative via TNFR2 [corrected] in the hippocampus and via TNFR1 [corrected] in the striatum after virus-induced encephalitis.
Rodriguez, Moses; Zoecklein, Laurie; Papke, Louisa; Gamez, Jeff; Denic, Aleksandar; Macura, Slobodan; Howe, Charles
Differentiating between injurious and reparative factors facilitates appropriate therapeutic intervention. We evaluated the role of tumor necrosis factor alpha (TNFalpha) in parenchymal brain pathology resolution following virus-induced encephalitis from a picornavirus, Theiler's murine encephalomyelitis virus (TMEV). We infected the following animals with TMEV for 7 to 270 days: B6/129 TNF(-/-) mice (without TNFalpha expression), B6/129 TNFR1(-/-) mice (without TNFalpha receptor 1 expression), and B6/129 TNFR2(-/-) mice (without TNFalpha receptor 2 expression). Normal TNFalpha-expressing controls were TMEV-infected B6, 129/J, B6/129F1 and B6/129F2 mice. Whereas all strains developed inflammation and neuronal injury in the hippocampus and striatum 7 to 21 days postinfection (dpi), the control mice resolved the pathology by 45 to 90 dpi. However, parenchymal hippocampal and striatal injury persisted in B6/129 TNF(-/-) mice following infection. Treating virus-infected mice with active recombinant mouse TNFalpha resulted in less hippocampal and striatal pathology, whereas TNFalpha-neutralizing treatment worsened pathology. T1 "black holes" appeared on MRI during early infection in the hippocampus and striatum in all mice but persisted only in TNF(-/-) mice. TNFR2 [corrected] mediated hippocampal pathology resolution whereas TNFR1 [corrected] mediated striatal healing. These findings indicate the role of TNFalpha in resolution of sublethal hippocampal and striatal injury. PMID:18422761
Induction Immunosuppression and Clinical Outcomes in Kidney Transplant Recipients Infected With Human Immunodeficiency Virus.
Kucirka, L M; Durand, C M; Bae, S; Avery, R K; Locke, J E; Orandi, B J; McAdams-DeMarco, M; Grams, M E; Segev, D L
There is an increased risk of acute rejection (AR) in human immunodeficiency virus-positive (HIV+) kidney transplant (KT) recipients. Induction immunosuppression is standard of care for those at high risk of AR; however, use in HIV+ patients is controversial, given fears of increased infection rates. We sought to compare clinical outcomes between HIV+ KT recipients who were treated with (i) anti-thymocyte globulin (ATG), (ii) IL-2 receptor blocker, and (iii) no induction. We studied 830 HIV+ KT recipients between 2000 and 2014, as captured in the Scientific Registry of Transplant Recipients, and compared rates of delayed graft function (DGF), AR, graft loss and death. Infections and hospitalizations were ascertained by International Classification of Diseases, Ninth Revision codes in a subset of 308 patients with Medicare. Compared with no induction, neither induction agent was associated with an increased risk of infection (weighted hazard ratio [wHR] 0.80, 95% confidence interval [CI] 0.55-1.18). HIV+ recipients who received induction spent fewer days in the hospital (weighted relative risk [wRR] 0.70, 95% CI 0.52-0.95), had lower rates of DGF (wRR 0.66, 95% CI 0.51-0.84), less graft loss (wHR 0.47, 95% CI 0.24-0.89) and a trend toward lower mortality (wHR 0.60, 95% CI 0.24-1.28). Those who received induction with ATG had lower rates of AR (wRR 0.59, 95% CI 0.35-0.99). Induction in HIV+ KT recipients was not associated with increased infections; in fact, those receiving ATG, the most potent agent, had the lowest rates. In light of the high risk of AR in this population, induction therapy should be strongly considered. PMID:27111897
Lucke, K; Reinking, U; el-Hifnawi, E; Dennin, R H; Laqua, H
The authors report on three patients with acute retinal necrosis who were treated with the virostatic agent Acyclovir and who underwent vitreoretinal surgery with silicone oil filling for total retinal detachment. In two eyes the retina was reattached, but useful vision was only preserved in one patient. Titers from blood and the vitreous, as well as microscopic findings in retinal biopsies, support the view that the necrosis is caused by a herpes simplex virus infection. After therapy with Acyclovir was instituted no further progression on the necrosis was observed. However, the development of retinal detachment could not be prevented. Early diagnosis and antiviral therapy are essential to improve the otherwise poor prognosis in this rare syndrome. PMID:3221657
Efficacy and Safety of Sofosbuvir-Based Antiviral Therapy to Treat Hepatitis C Virus Infection After Kidney Transplantation.
Kamar, N; Marion, O; Rostaing, L; Cointault, O; Ribes, D; Lavayssière, L; Esposito, L; Del Bello, A; Métivier, S; Barange, K; Izopet, J; Alric, L
There is no approved therapy for hepatitis C virus (HCV) infection after kidney transplantation, and no data regarding the use of new-generation direct antiviral agents (DAAs) have been published so far. The aims of this pilot study were to assess the efficacy and safety of an interferon-free sofosbuvir-based regimen to treat chronic HCV infection in kidney transplant recipients. Twenty-five kidney transplant recipients with chronic HCV infection were given, for 12 (n = 19) or 24 weeks (n = 6), sofosbuvir plus ribavirin (n = 3); sofosbuvir plus daclatasvir (n = 4); sofosbuvir plus simeprevir, with (n = 1) or without ribavirin (n = 6); sofosbuvir plus ledipasvir, with (n = 1) or without ribavirin (n = 9); and sofosbuvir plus pegylated-interferon plus ribavirin (n = 1). A rapid virological response, defined by undetectable viremia at week 4 after starting DAA therapy, was observed in 22 of the 25 patients (88%). At the end of therapy, HCV RNA was undetectable in all patients. At 4 and 12 weeks after completing DAA therapy, all had a sustained virological response. The tolerance to anti-HCV therapy was excellent and no adverse event was observed. A significant decrease in calcineurin inhibitor levels was observed after HCV clearance. New-generation oral DAAs are efficient and safe to treat HCV infection after kidney transplantation. PMID:26587971
Mortality Caused by Bath Exposure of Zebrafish (Danio rerio) Larvae to Nervous Necrosis Virus Is Limited to the Fourth Day Postfertilization.
Morick, Danny; Faigenbaum, Or; Smirnov, Margarita; Fellig, Yakov; Inbal, Adi; Kotler, Moshe
Nervous necrosis virus (NNV) is a member of the Betanodavirus genus that causes fatal diseases in over 40 species of fish worldwide. Mortality among NNV-infected fish larvae is almost 100%. In order to elucidate the mechanisms responsible for the susceptibility of fish larvae to NNV, we exposed zebrafish larvae to NNV by bath immersion at 2, 4, 6, and 8 days postfertilization (dpf). Here, we demonstrate that developing zebrafish embryos are resistant to NNV at 2 dpf due to the protection afforded by the egg chorion and, to a lesser extent, by the perivitelline fluid. The zebrafish larvae succumbed to NNV infection during a narrow time window around the 4th dpf, while 6- and 8-day-old larvae were much less sensitive, with mortalities of 24% and 28%, respectively. PMID:25746990
Sequence similarities of the capsid gene of Chilean and European isolates of infectious pancreatic necrosis virus point towards a common origin.
Mutoloki, Stephen; Evensen, Øystein
The Chilean salmonid industry was developed by importing breeding materials, a practice still in effect due to deficits in the national supply of roe. Importation of breeding materials is often associated with the transmission of pathogens. The objectives of this study were to compare the infectious pancreatic necrosis virus (IPNV) isolates from Chile to those of European origin and to determine the diversity of the Chilean IPNV. The VP2 genes of IPNV from Chilean fish (whose eggs originated from Scotland, Iceland and Norway) were compared to isolates from fish in Norway and Ireland. The results show that the isolates are identical (97-99%) and cluster into one genogroup. Our findings support previous reports of association between the trade-in breeding materials and transmission of pathogens. Furthermore, our results demonstrate the genotypic diversity of Chilean IPNV isolates. These findings have important implications for IPNV disease diagnosis and control in Chile. PMID:21402593
Mortality Caused by Bath Exposure of Zebrafish (Danio rerio) Larvae to Nervous Necrosis Virus Is Limited to the Fourth Day Postfertilization
Morick, Danny; Faigenbaum, Or; Smirnov, Margarita; Fellig, Yakov; Inbal, Adi
Nervous necrosis virus (NNV) is a member of the Betanodavirus genus that causes fatal diseases in over 40 species of fish worldwide. Mortality among NNV-infected fish larvae is almost 100%. In order to elucidate the mechanisms responsible for the susceptibility of fish larvae to NNV, we exposed zebrafish larvae to NNV by bath immersion at 2, 4, 6, and 8 days postfertilization (dpf). Here, we demonstrate that developing zebrafish embryos are resistant to NNV at 2 dpf due to the protection afforded by the egg chorion and, to a lesser extent, by the perivitelline fluid. The zebrafish larvae succumbed to NNV infection during a narrow time window around the 4th dpf, while 6- and 8-day-old larvae were much less sensitive, with mortalities of 24% and 28%, respectively. PMID:25746990
Identification of the major capsid protein of erythrocytic necrosis virus (ENV) and development of quantitative real-time PCR assays for quantification of ENV DNA.
Purcell, Maureen K; Pearman-Gillman, Schuyler; Thompson, Rachel L; Gregg, Jacob L; Hart, Lucas M; Winton, James R; Emmenegger, Eveline J; Hershberger, Paul K
Viral erythrocytic necrosis (VEN) is a disease of marine and anadromous fish that is caused by the erythrocytic necrosis virus (ENV), which was recently identified as a novel member of family Iridoviridae by next-generation sequencing. Phylogenetic analysis of the ENV DNA polymerase grouped ENV with other erythrocytic iridoviruses from snakes and lizards. In the present study, we identified the gene encoding the ENV major capsid protein (MCP) and developed a quantitative real-time PCR (qPCR) assay targeting this gene. Phylogenetic analysis of the MCP gene sequence supported the conclusion that ENV does not group with any of the currently described iridovirus genera. Because there is no information regarding genetic variation of the MCP gene across the reported host and geographic range for ENV, we also developed a second qPCR assay for a more conserved ATPase-like gene region. The MCP and ATPase qPCR assays demonstrated good analytical and diagnostic sensitivity and specificity based on samples from laboratory challenges of Pacific herring Clupea pallasii The qPCR assays had similar diagnostic sensitivity and specificity as light microscopy of stained blood smears for the presence of intraerythrocytic inclusion bodies. However, the qPCR assays may detect viral DNA early in infection prior to the formation of inclusion bodies. Both qPCR assays appear suitable for viral surveillance or as a confirmatory test for ENV in Pacific herring from the Salish Sea. PMID:27154315
Identification of the major capsid protein of erythrocytic necrosis virus (ENV) and development of quantitative real-time PCR assays for quantification of ENV DNA
Purcell, Maureen K.; Pearman-Gillman, Schuyler; Thompson, Rachel L.; Gregg, Jacob L.; Hart, Lucas M.; Winton, James R.; Emmenegger, Eveline J.; Hershberger, Paul K.
Viral erythrocytic necrosis (VEN) is a disease of marine and anadromous fish that is caused by the erythrocytic necrosis virus (ENV), which was recently identified as a novel member of family Iridoviridae by next-generation sequencing. Phylogenetic analysis of the ENV DNA polymerase grouped ENV with other erythrocytic iridoviruses from snakes and lizards. In the present study, we identified the gene encoding the ENV major capsid protein (MCP) and developed a quantitative real-time PCR (qPCR) assay targeting this gene. Phylogenetic analysis of the MCP gene sequence supported the conclusion that ENV does not group with any of the currently described iridovirus genera. Because there is no information regarding genetic variation of the MCP gene across the reported host and geographic range for ENV, we also developed a second qPCR assay for a more conserved ATPase-like gene region. The MCP and ATPase qPCR assays demonstrated good analytical and diagnostic sensitivity and specificity based on samples from laboratory challenges of Pacific herring Clupea pallasii. The qPCR assays had similar diagnostic sensitivity and specificity as light microscopy of stained blood smears for the presence of intraerythrocytic inclusion bodies. However, the qPCR assays may detect viral DNA early in infection prior to the formation of inclusion bodies. Both qPCR assays appear suitable for viral surveillance or as a confirmatory test for ENV in Pacific herring from the Salish Sea.
Whole-Body Analysis of a Viral Infection: Vascular Endothelium is a Primary Target of Infectious Hematopoietic Necrosis Virus in Zebrafish Larvae
Torhy, Corinne; Briolat, Valérie; Colucci-Guyon, Emma; Brémont, Michel; Herbomel, Philippe; Boudinot, Pierre; Levraud, Jean-Pierre
The progression of viral infections is notoriously difficult to follow in whole organisms. The small, transparent zebrafish larva constitutes a valuable system to study how pathogens spread. We describe here the course of infection of zebrafish early larvae with a heat-adapted variant of the Infectious Hematopoietic Necrosis Virus (IHNV), a rhabdovirus that represents an important threat to the salmonid culture industry. When incubated at 24°C, a permissive temperature for virus replication, larvae infected by intravenous injection died within three to four days. Macroscopic signs of infection followed a highly predictable course, with a slowdown then arrest of blood flow despite continuing heartbeat, followed by a loss of reactivity to touch and ultimately by death. Using whole-mount in situ hybridization, patterns of infection were imaged in whole larvae. The first infected cells were detectable as early as 6 hours post infection, and a steady increase in infected cell number and staining intensity occurred with time. Venous endothelium appeared as a primary target of infection, as could be confirmed in fli1:GFP transgenic larvae by live imaging and immunohistochemistry. Disruption of the first vessels took place before arrest of blood circulation, and hemorrhages could be observed in various places. Our data suggest that infection spread from the damaged vessels to underlying tissue. By shifting infected fish to a temperature of 28°C that is non-permissive for viral propagation, it was possible to establish when virus-generated damage became irreversible. This stage was reached many hours before any detectable induction of the host response. Zebrafish larvae infected with IHNV constitute a vertebrate model of an hemorrhagic viral disease. This tractable system will allow the in vivo dissection of host-virus interactions at the whole organism scale, a feature unrivalled by other vertebrate models. PMID:21304884
Mechanisms for virus-induced liver disease: tumor necrosis factor-mediated pathology independent of natural killer and T cells during murine cytomegalovirus infection.
Orange, J S; Salazar-Mather, T P; Opal, S M; Biron, C A
The contribution of endogenous NK cells and cytokines to virus-induced liver pathology was evaluated during murine cytomegalovirus infections of mice. In immunocompetent C57BL/6 mice, the virus induced a self-limited liver disease characterized by hepatitis, with focal inflammation, and large grossly visible subcapsular necrotic foci. The inflammatory foci were most numerous and contained the greatest number of cells 3 days after infection; they colocalized with areas of viral antigen expression. The largest number of necrotic foci was found 2 days after infection. Overall hepatic damage, assessed as increased expression of liver enzymes in serum, accompanied the development of inflammatory and necrotic foci. Experiments with neutralizing antibodies demonstrated that although virus-induced tumor necrosis factor (TNF) can have antiviral effects, it also mediated significant liver pathology. TNF was required for development of hepatic necrotic foci and increased levels of liver enzymes in serum but not for increased numbers of inflammatory foci. The necrotic foci and liver enzyme indications of pathology occurred independently of NK and T cells, because mice rendered NK-cell deficient by treatment with antibodies, T- and B-cell-deficient Rag-/- mice, and NK- and T-cell-deficient E26 mice all manifested both parameters of disease. Development of necrotic foci and maximally increased levels of liver enzymes in serum also were TNF dependent in NK-cell-deficient mice. Moreover, in the immunodeficient E26 mice, virus-induced liver disease was progressive, with eventual death of the host, and neutralization of TNF significantly increased longevity. These results establish conditions separating hepatitis from significant liver damage and demonstrate a cytokine-mediated component to viral pathogenesis. PMID:9371583
Epidemiological investigation of infectious hematopoietic necrosis virus in salt water net-pen reared Atlantic salmon in British Columbia, Canada
St-Hilaire, Sophie; Ribble, Carl S.; Stephen, Craig; Anderson, Eric; Kurath, Gael; Kent, Michael L.
The presentation of IHNV on farms, the spatial and temporal patterns of the outbreaks between 1992 and 1996, and the genetic similarity between isolates collected from nine outbreaks spanning a 5-year period, all supported the plausibility of farm-to-farm spread of the virus. Furthermore, the marked decrease in the incidence rate of IHN in farmed Atlantic salmon after the implementation of an area-based management plan aimed at reducing farm-to-farm spread of the virus also supported this hypothesis. Although the source of IHNV for the index case was not determined in this study, secondary spread of the virus between farms via management practices, such as movement of fish, co-habiting naı̈ve fish with survivors of the viral disease, and movement of equipment, likely accounted for some farm outbreaks. This suggested that many cases of IHN may be preventable using good on-farm biosecurity.
Cortical necrosis in a renal transplant
Blumhardt, R.; Growcock, G.; Lasher, J.C.
The /sup 99m/Tc-DTPA renogram is a well extabished noninvasive method for evaluating and following transplanted kidneys. The examination is useful in distinguishing rejection from acute tubular necrosis as well as demonstrating several less common complications such as vascular occlusion, urinary extravasation, obstruction, and lymphocele. A previously unreported condition involving a transplant kidney (i.e., renal cortical necrosis) is described which was diagnosed with renal scintigraphy in combination with sonography.
[Kidney bean "Pervomayskaya" as the indicator plant for tobacco mosaic virus].
Kraiev, V H
It was shown that garden beans of "Pervomayskaya" variety respond to mechanical inoculation of leaves with tobacco mosaic virus by formation of local lesions, and thus it may be the indicator plant for the virus. PMID:16250238
Proteomic analysis of differentially expressed protein in hemocytes of wild giant freshwater prawn Macrobrachium rosenbergii infected with infectious hypodermal and hematopoietic necrosis virus (IHHNV)
Alinejad, T.; Bin, Kwong Q.; Vejayan, J.; Othman, R.Y.; Bhassu, S.
Epizootic diseases cause huge mortality and economical loses at post larvae stages in freshwater prawn aquaculture industry. These prawns seem less susceptible to viral diseases except for infectious hypodermal and hematopoietic necrosis virus (IHHNV). During viral infection in prawns, hemocytes are the primary organ that shows immunological response within the early stages of infection. We applied proteomic approaches to understand differential expression of the proteins in hemocytes during the viral disease outbreak. To aid the goal, we collected Macrobrachium rosenbergii broodstocks from the local grow out hatchery which reported the first incidence of IHHNV viral outbreak during larvae stage. Primarily, application of the OIE primer targeting 389 bp fragments of IHHNV virus was used in identification of the infected and non-infected samples of the prawn breeding line. Analysis of two-dimensional gel electrophoresis showed specific down-regulation of Arginine kinase and Sarcoplasmic calcium-binding protein and up/down-regulation of Prophenoloxidase1 and hemocyanin isoforms. These proteins were validated using semi quantitative RT-PCR and gene transcripts at mRNA level. These identified proteins can be used as biomarkers, providing a powerful approach to better understanding of the immunity pathway of viral disease with applications in analytic and observational epidemiology diagnosis. Proteomic profiling allows deep insight into the pathogenesis of IHHNV molecular regulation and mechanism of hemocyte in freshwater prawns. PMID:26106581
Proteomic analysis of differentially expressed protein in hemocytes of wild giant freshwater prawn Macrobrachium rosenbergii infected with infectious hypodermal and hematopoietic necrosis virus (IHHNV).
Alinejad, T; Bin, Kwong Q; Vejayan, J; Othman, R Y; Bhassu, S
Epizootic diseases cause huge mortality and economical loses at post larvae stages in freshwater prawn aquaculture industry. These prawns seem less susceptible to viral diseases except for infectious hypodermal and hematopoietic necrosis virus (IHHNV). During viral infection in prawns, hemocytes are the primary organ that shows immunological response within the early stages of infection. We applied proteomic approaches to understand differential expression of the proteins in hemocytes during the viral disease outbreak. To aid the goal, we collected Macrobrachium rosenbergii broodstocks from the local grow out hatchery which reported the first incidence of IHHNV viral outbreak during larvae stage. Primarily, application of the OIE primer targeting 389 bp fragments of IHHNV virus was used in identification of the infected and non-infected samples of the prawn breeding line. Analysis of two-dimensional gel electrophoresis showed specific down-regulation of Arginine kinase and Sarcoplasmic calcium-binding protein and up/down-regulation of Prophenoloxidase1 and hemocyanin isoforms. These proteins were validated using semi quantitative RT-PCR and gene transcripts at mRNA level. These identified proteins can be used as biomarkers, providing a powerful approach to better understanding of the immunity pathway of viral disease with applications in analytic and observational epidemiology diagnosis. Proteomic profiling allows deep insight into the pathogenesis of IHHNV molecular regulation and mechanism of hemocyte in freshwater prawns. PMID:26106581
Evaluation of the protective immunogencity of the N, P, M, NV and G proteins of infectious hematopoietic necrosis virus in rainbow trout Oncorhynchus mykiss using DNA vaccines
Corbeil, S.; LaPatra, S.E.; Anderson, E.D.; Jones, J.; Vincent, B.; Hsu, Y.-L; Kurath, G.
The protective immunogenicity of the nucleoprotein (N), phosphoprotein (P), matrix protein (M), non-virion protein (NV) and glycoprotein (G) of the rhabdovirus infectious hematopoietic necrosis virus (IHNV) was assessed in rainbow trout using DNA vaccine technology. DNA vaccines were produced by amplifying and cloning the viral genes in the plasmid pCDNA 3.1. The protective immunity elicited by each vaccine was evaluated through survival of immunized fry after challenge with live virus. Neutralizing antibody titers were also determined in vaccinated rainbow troutOncorhynchus mykiss fry (mean weight 2 g) and 150 g sockeye salmon Oncorhynchus nerka. The serum from the 150 g fish was also used in passive immunization studies with naïve fry. Our results showed that neither the internal structural proteins (N, P and M) nor the NV protein of IHNV induced protective immunity in fry or neutralizing antibodies in fry and 150 g fish when expressed by a DNA vaccine construct. The G protein, however, did confer significant protection in fry up to 80 d post-immunization and induced protective neutralizing antibodies. We are currently investigating the role of different arms of the fish immune system that contribute to the high level of protection against IHNV seen in vaccinated fish.
... Germ Cell Tumors Kidney/Wilms Tumor Liver Cancer Neuroblastoma Osteosarcoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma Thyroid ... Tumor Liver Cancer Lymphoma (Non-Hodgkin) Lymphoma (Hodgkin) Neuroblastoma Osteosarcoma Retinoblastoma Rhabdomyosarcoma Skin Cancer Soft Tissue Sarcoma ...
The impact of surveillance and rapid reduction in immunosuppression to control BK virus-related graft injury in kidney transplantation.
Elfadawy, Nissreen; Flechner, Stuart M; Liu, Xiaobo; Schold, Jesse; Tian, Devin; Srinivas, Titte R; Poggio, Emilio; Fatica, Richard; Avery, Robin; Mossad, Sherif B
We prospectively screened 609 consecutive kidney (538) and kidney-pancreas (71) transplant recipients for BK viremia over a 4-year interval using polymerase chain reaction viral load detection and protocol kidney biopsies. We found that BK viremia is common at our center: total cases 26.7%, cases during first year 21.3% (mean 4 months), and recipients with ≥ 10 000 copies/ml 12.3%. We found few predictive clinical or demographic risk factors for any BK viremia or viral loads ≥ 10,000 copies/ml, other than prior treatment of biopsy confirmed acute rejection and/or higher immunosuppressive blood levels of tacrolimus (P = 0.001) or mycophenolate mofetil (P = 0.007). Viral loads at diagnosis (<10 000 copies/ml) demonstrated little impact on graft function or survival. However, rising copy numbers demand early reductions in immunosuppressive drug doses of at least 30-50%. Viral loads >185 000 copies/ml at diagnosis were predictive of BK virus-associated nephropathy (BKVAN; OR: 113.25, 95% CI: 17.22-744.6, P < 0.001). Surveillance for BK viremia and rapid reduction of immunosuppression limited the incidence of BKVAN to 1.3%. The addition of leflunomide or ciprofloxacin to immunosuppressive dose reduction did not result in greater rates of viral clearance. These data support the role of early surveillance for BK viremia to limit the impact on transplant outcome, although the most effective schedule for screening awaits further investigation. PMID:23763289
Recognition of Linear B-Cell Epitope of Betanodavirus Coat Protein by RG-M18 Neutralizing mAB Inhibits Giant Grouper Nervous Necrosis Virus (GGNNV) Infection
Chen, Chien-Wen; Wu, Ming-Shan; Huang, Yi-Jen; Cheng, Chao-An; Chang, Chi-Yao
Betanodavirus is a causative agent of viral nervous necrosis syndrome in many important aquaculture marine fish larvae, resulting in high global mortality. The coat protein of Betanodavirus is the sole structural protein, and it can assemble the virion particle by itself. In this study, we used a high-titer neutralizing mAB, RG-M18, to identify the linear B-cell epitope on the viral coat protein. By mapping a series of recombinant proteins generated using the E. coli PET expression system, we demonstrated that the linear epitope recognized by RG-M18 is located at the C-terminus of the coat protein, between amino acid residues 195 and 338. To define the minimal epitope region, a set of overlapping peptides were synthesized and evaluated for RG-M18 binding. Such analysis identified the 195VNVSVLCR202 motif as the minimal epitope. Comparative analysis of Alanine scanning mutagenesis with dot-blotting and ELISA revealed that Valine197, Valine199, and Cysteine201 are critical for antibody binding. Substitution of Leucine200 in the RGNNV, BFNNV, and TPNNV genotypes with Methionine200 (thereby simulating the SJNNV genotype) did not affect binding affinity, implying that RG-M18 can recognize all genotypes of Betanodaviruses. In competition experiments, synthetic multiple antigen peptides of this epitope dramatically suppressed giant grouper nervous necrosis virus (GGNNV) propagation in grouper brain cells. The data provide new insights into the protective mechanism of this neutralizing mAB, with broader implications for Betanodavirus vaccinology and antiviral peptide drug development. PMID:25938761
Evaluation of a Subunit Vaccine to Infectious Hematopoietic Necrosis Virus, July 31, 1988 to September 20, 1989 Annual Report.
Leong, JoAnn Ching
A recombinant DNA vaccine to IHNV was prepared and tested in field trials at Clear Springs Trout Company's Box Canyon Hatchery in Buhl, Idaho this year in Phase III of the project. The vaccine under consideration in these field trials consisted of lysed bacteria that contained a plasmid which expressed an antigenic portion of the IHNV glycoprotein. In addition, laboratory trials with a bacterial expressed viral nucleoprotein indicated that this served as an immune adjuvant. Therefore, a decision was made to conduct these field trials on a vaccine containing both IHNV glycoprotein and IHNV nucleoprotein. Original plans to conduct the field trial at Dworshak National Fish Hatchery were canceled because a management decision was made by Dworshak Fish and Wildlife personnel to rear steelhead salmon eggs from IHNV positive parents at Kooskia National Fish Hatchery. This decision, which was made without prior notification to us, resulted in some discussion at the IHNV committee meeting convened by the Fish and Wildlife Service in Moscow, Idaho on April 27, 1989. At that time, the authors dismay at this decision was voiced and the prediction that an outbreak of IHNV would occur at Kooskia was made. In less than a week, a massive IHNV outbreak did occur at Kooskia and plans to run a field trial at this facility had to be discarded. An alternative site was found at the Box Canyon Hatchery site of Clear Springs Trout Company. Dr. Robert Busch, Director of Research and Development for Clear Springs Trout Company, offered the use of the site. In preparation for the site change they consulted Mary Buckman, Oregon Department of Fish and Wildlife statistician, and they obtained a sample of the IHN virus present at Box Canyon. The Box Canyon virus isolate was typed by reactivity with monoclonal antibodies by Dr. Sandra Ristow at Washington State University. There was insufficient time to examine the vaccine efficacy with the Box Canyon virus isolate in laboratory trials and they
Influence of herpes simplex virus infection on benzo(a)pyrene metabolism in monkey kidney cells
Degenhardt, J.H.; Whitcomb, B.; Hall, M.R.
Current research in our laboratory is designed to investigate the intracellular interactions of BP with oncogenic DNA viruses of animals and humans. In this study, our purpose was to determine whether BP is metabolized in herpes simplex virus type 2 (HSV-2) infected cells and whether HSV-2 infection affects intracellular levels of the aryl hydrocarbon hydroxylase system necessary for BP metabolism.
Titre distribution patterns of infectious haematopoietic necrosis virus in ovarian fluids of hatchery and feral salmon populations
Mulcahy, D.; Pascho, R.J.; Jenes, C.K.
Infectious haematopoietic mecrosis virus (IHNV) is enzootic in virtually all populations of sockeye salmon, Oncorhynchus nerka (Walbaum), and in populations of chinook salmon, O. 1shawytscha (Walbaum), of the Sacramento River drainage in California. This disease is an obstacle in hatcheries using brood stocks from these populations. However, naturally spawning sockeye salmon are highly successful and are the most important commercially fished salmon species in the United States. Most of the commercial landings of sockeye salmon are of feral fish originating in Alaska. The success of natural populations of salmon in which IHNV is enzootic, and the recurrent outbreaks of the disease in hatchery fish, led us to compare IHNW prevalence rates in hatchery and feral salmon populations.
Genetic diversity of infectious hematopoietic necrosis virus from Feather River and Lake Oroville, California, and virulence of selected isolates for Chinook salmon and rainbow trout
Bendorf, C.M.; Kelley, G.O.; Yun, S.C.; Kurath, G.; Andree, K.B.; Hedrick, R.P.
Infectious hematopoietic necrosis virus (IHNV) is a significant pathogen of young salmonid fishes worldwide but particularly within the historical range of the Pacific Northwest and California. In the Sacramento and San Joaquin River drainages of California, IHNV outbreaks in juvenile Chinook salmon Oncorhynchus tshawytscha have been observed regularly at large production hatcheries, including Coleman National Fish Hatchery (established in 1941) and Feather River State Fish Hatchery (FRH; established in 1967), since facility operations began. Recent severe epidemics at the FRH in 1998 and 2000-2002 prompted investigations into the characteristics and potential sources of virus at this facility. Both phylogenetic analyses of a variable portion of the glycoprotein gene and serologic comparisons based on neutralization with three polyclonal rabbit sera were used to characterize 82 IHNV isolates from the Feather River watershed between 1969 and 2004. All isolates examined were in the L genogroup and belonged to one of three serologic groups typical of IHNV from California. The IHNV isolates from the Feather River area demonstrated a maximum nucleotide sequence divergence of 4.0%, and new isolates appeared to emerge from previous isolates rather than by the introduction of more diverse subgroups from exogenous sources. The earliest isolates examined from the watershed formed the subgroup LI, which disappeared coincidently with a temporal shift to new genetic and serologic types of the larger subgroup LII. Experimental challenges demonstrated no significant differences in the virulence for juvenile Chinook salmon and rainbow trout O. mykiss from selected isolates representing the principal types of IHNV found historically and from recent epidemics at FRH. While most isolates were equally virulent for both host species, one isolate was found to be more virulent for Chinook salmon than for rainbow trout. ?? Copyright by the American Fisheries Society 2007.
Infection of peripheral blood mononuclear cells by herpes simplex and Epstein-Barr viruses. Differential induction of interleukin 6 and tumor necrosis factor-alpha.
Gosselin, J; Flamand, L; D'Addario, M; Hiscott, J; Menezes, J
Infection by herpesviruses can result in profound immunosuppressive or immunomodulatory effects. However, no significant information is available on the effect of such infections on the production of immunoregulatory cytokines. We studied the kinetics of production of two monocyte-derived cytokines, interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF alpha), induced by Epstein-Barr virus (EBV) and herpes simplex virus type 1 (HSV-1) in peripheral blood mononuclear cell cultures and in fractionated cell populations. We observed that, when compared to HSV-1, EBV is a stronger inducer of IL-6. In EBV-infected cultures, IL-6 protein was detected at day 1 postinfection and gradually increased with time. In contrast, lower amounts of IL-6 were detected 5 d postinfection in HSV-1-infected cultures. HSV-1-infected cultures secreted significant amounts of TNF alpha protein after 5 d of culture and reached a maximal level of production at day 7, whereas EBV inhibited TNF alpha production. In fractionated cell populations, monocytic cells were found to be the main source of IL-6 synthesis after EBV or HSV-1 infection. However, TNF alpha synthesis in HSV-1-infected cultures was from both B and monocytic cells. By using the polymerase chain reaction technique we show that, after infection by these two herpesviruses, differences in cytokine gene products are also observed at the transcriptional level. These observations demonstrate that EBV and HSV-1 exert differential effects on IL-6 and TNF alpha gene transcription and on the resulting protein secretion in human mononuclear blood cells. Images PMID:1318324
Immunogenicity and Cross Protective Ability of the Central VP2 Amino Acids of Infectious Pancreatic Necrosis Virus in Atlantic Salmon (Salmo salar L.)
Munang'andu, Hetron M.; Sandtrø, Ane; Mutoloki, Stephen; Brudeseth, Bjørn E.; Santi, Nina; Evensen, Øystein
Infectious pancreatic necrosis virus (IPNV) is a member of the family Birnaviridae that has been linked to high mortalities in juvenile salmonids and postsmolt stages of Atlantic salmon (Salmo salar L.) after transfer to seawater. IPN vaccines have been available for a long time but their efficacy has been variable. The reason for the varying immune response to these vaccines has not well defined and studies on the importance of using vaccine trains homologous to the virulent field strain has not been conclusive. In this study we prepared one vaccine identical to the virulent Norwegian Sp strain NVI-015 (NCBI: 379740) (T217A221T247 of VP2) and three other vaccine strains developed using the same genomic backbone altered by reverse genetics at three residues yielding variants, T217T221T247, P217A221A247, P217T221A247. These 4 strains, differing in these three positions only, were used as inactivated, oil-adjuvanted vaccines while two strains, T217A221T247 and P217T221A247, were used as live vaccines. The results show that these three residues of the VP2 capsid play a key role for immunogenicity of IPNV vaccines. The virulent strain for inactivated vaccines elicited the highest level of virus neutralization (VN) titers and ELISA antibodies. Interestingly, differences in immunogenicity were not reflected in differences in post challenge survival percentages (PCSP) for oil-adjuvanted, inactivated vaccines but clearly so for live vaccines (TAT and PTA). Further post challenge viral carrier state correlated inversely with VN titers at challenge for inactivated vaccines and prevalence of pathology in target organs inversely correlated with protection for live vaccines. Overall, our findings show that a few residues localized on the VP2-capsid are important for immunogenicity of IPNV vaccines. PMID:23349841
Strand-specific, real-time RT-PCR assays for quantification of genomic and positive-sense RNAs of the fish rhabdovirus, Infectious hematopoietic necrosis virus
Purcell, Maureen K.; Hart, S. Alexandra; Kurath, Gael; Winton, James R.
The fish rhabdovirus, Infectious hematopoietic necrosis virus (IHNV), is an important pathogen of salmonids. Cell culture assays have traditionally been used to quantify levels of IHNV in samples; however, real-time or quantitative RT-PCR assays have been proposed as a rapid alternative. For viruses having a single-stranded, negative-sense RNA genome, standard qRT-PCR assays do not distinguish between the negative-sense genome and positive-sense RNA species including mRNA and anti-genome. Thus, these methods do not determine viral genome copy number. This study reports development of strand-specific, qRT-PCR assays that use tagged primers for enhancing strand specificity during cDNA synthesis and quantitative PCR. Protocols were developed for positive-strand specific (pss-qRT-PCR) and negative-strand specific (nss-qRT-PCR) assays for IHNV glycoprotein (G) gene sequences. Validation with synthetic RNA transcripts demonstrated the assays could discriminate the correct strand with greater than 1000-fold fidelity. The number of genome copies in livers of IHNV-infected fish determined by nss-qRT-PCR was, on average, 8000-fold greater than the number of infectious units as determined by plaque assay. We also compared the number of genome copies with the quantity of positive-sense RNA and determined that the ratio of positive-sense molecules to negative-sense genome copies was, on average, 2.7:1. Potential future applications of these IHNV strand-specific qRT-PCR assays are discussed.
Susceptibility of ocean- and stream-type Chinook salmon to isolates of the L, U, and M genogroups of infectious hematopoietic necrosis virus (IHNV).
Hernandez, Daniel G; Purcell, Maureen K; Friedman, Carolyn S; Kurath, Gael
This study examined the susceptibility of Chinook salmon Oncorhynchus tshawytscha to viral strains from the L, U, and M genogroups of infectious hematopoietic necrosis virus (IHNV) present in western North America. The goal of this investigation was to establish a baseline understanding of the susceptibility of ocean- and stream-type Chinook salmon to infection and mortality caused by exposure to commonly detected strains of L, U, and M IHNV. The L IHNV strain tested here was highly infectious and virulent in both Chinook salmon populations, following patterns previously reported for Chinook salmon. Furthermore, ocean- and stream-type Chinook salmon fry at 1 g can also become subclinically infected with U and M strains of IHNV without experiencing significant mortality. The stream-type life history phenotype was generally more susceptible to infection and suffered greater mortality than the ocean-type phenotype. Between the U and M genogroup strains tested, the U group strains were generally more infectious than the M group strains in both Chinook salmon types. Substantial viral clearance occurred by 30 d post exposure, but persistent viral infection was observed with L, U, and M strains in both host populations. While mortality decreased with increased host size in stream-type Chinook salmon, infection prevalence was not lower for all strains at a greater size. These results suggest that Chinook salmon may serve as reservoirs and/or vectors of U and M genogroup IHNV. PMID:27596856
Detection and genetic profiling of infectious hypodermal and haematopoietic necrosis virus (IHHNV) infections in wild berried freshwater prawn, Macrobrachium rosenbergii collected for hatchery production.
Hazreen Nita, M K; Kua, B C; Bhassu, S; Othman, R Y
Infectious hypodermal and haematopoietic necrosis virus (IHHNV) has been detected widely in penaeid culture facilities in Asia and the Americas. IHHNV infection on sub-adult and postlarvae of the giant freshwater prawn, Macrobrachium rosenbergii which had caused up to 80% mortalities was first reported in Southeast Taiwan in 2006. In Malaysia, although, there has been no report on IHHNV infections in M. rosenbergii, preliminary work suggests that there is an urgent need to setup a screening protocol for IHHNV for both wild and cultured populations. In this study, polymerase chain reaction based screening was carried out on 30 randomly sampled berried wild M. rosenbergii before and after spawning. All samples did not showed any sign of IHHNV infection. However, the results showed that 20% of the samples were IHHNV positive. Sequence analysis of the amplified band using NCBI-BLAST showed that the putative IHHNV sequence had 98% nucleotide sequence (388 bp) identity with the IHHNV isolate AC-05-005 non-structural protein 1 gene and seven other IHHNV strains in the data bank further affirming the suggestion on the presence of IHHNV in wild freshwater prawn populations in Malaysia. PMID:21755294
Administration of recombinant Reishi immunomodulatory protein (rLZ-8) diet enhances innate immune responses and elicits protection against nervous necrosis virus in grouper Epinephelus coioides.
Kuan, Yen-Chou; Sheu, Fuu; Lee, Guo-Chi; Tsai, Ming-Wei; Hung, Chih-Liang; Nan, Fan-Hua
Nervous necrosis virus (NNV) infection during larvae and juvenile stage in grouper (Epinephelus coioides) has caused severe economic losses in the aquaculture industry in Asia. The aims of this study were to evaluate the influence of recombinant Reishi protein, rLZ-8, on the innate immune responses and the viral resisting ability in fish. Groupers were fed with rLZ-8 supplemented diet (1.25-37.5 mg (rLZ-8)/kg(diet)), and the cytokine gene expression, innate immune responses, and survival rate after NNV challenge were examined. The fish fed with rLZ-8 diet showed 6- to 11-fold upregulated TNF-α and IL-1β gene expression, along with significant increased respiratory burst and phagocytic activity. Moreover, feeding the fish with 37.5 mg/kg rLZ-8 diet elicited significant improvement in post viral challenge survival rate (85.7%). These discoveries indicated that rLZ-8 could be utilized as an ant-pathogen immunostimulant, and provided a new candidate to fight against NNV infection in fish. PMID:22366063
Human Immunodeficiency Virus Type 1 Subtype C Tat Fails To Induce Intracellular Calcium Flux and Induces Reduced Tumor Necrosis Factor Production from Monocytes▿
Campbell, Grant R.; Watkins, Jennifer D.; Singh, Kumud K.; Loret, Erwann P.; Spector, Stephen A.
Over 50% of all human immunodeficiency virus type 1 (HIV-1) infections worldwide are caused by subtype C strains, yet most research to date focuses on subtype B, the subtype most commonly found in North America and Europe. The HIV-1 trans-acting regulatory protein (Tat) is essential for regulating productive replication of HIV-1. Tat is secreted by HIV-infected cells and alters several functions of uninfected bystander cells. One such function is that, by acting at the cell membrane, subtype B Tat stimulates the production of tumor necrosis factor (TNF) and chemokine (C-C motif) ligand 2 (CCL2) from human monocytes and can act as a chemoattractant. In this study, we show that the mutation of a cysteine to a serine at residue 31 of Tat commonly found in subtype C variants significantly inhibits the abilities of the protein to bind to chemokine (C-C motif) receptor 2 (CCR2), induce intracellular calcium flux, stimulate TNF and CCL2 production, and inhibit its chemoattractant properties. We also show that TNF is important in mediating some effects of extracellular Tat. This report therefore demonstrates the important functional differences between subtype C and subtype B Tat and highlights the need for further investigation into the different strains of HIV-1. PMID:17376903
Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection
Lin, Ming V.; Sise, Meghan E.; Pavlakis, Martha; Amundsen, Beth M.; Chute, Donald; Rutherford, Anna E.; Chung, Raymond T.; Curry, Michael P.; Hanifi, Jasmine M.; Gabardi, Steve; Chandraker, Anil; Heher, Eliot C.; Elias, Nahel; Riella, Leonardo V.
The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34–70 years), median creatinine of 1.2 mg/dL (0.66–1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in
Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection.
Lin, Ming V; Sise, Meghan E; Pavlakis, Martha; Amundsen, Beth M; Chute, Donald; Rutherford, Anna E; Chung, Raymond T; Curry, Michael P; Hanifi, Jasmine M; Gabardi, Steve; Chandraker, Anil; Heher, Eliot C; Elias, Nahel; Riella, Leonardo V
The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney
[Development of rapid detection of infectious hypodermal and hematopoietic necrosis virus by loop-mediated isothermal amplification].
He, Lin; Xu, Hai-Sheng; Wang, Mei-Zhen; Rong, Hua-Nan
Loop-mediated isothermal amplification (LAMP) assay is a novel method of gene amplification with high specificity, sensitivity and rapidity, which can be applied for disease diagnosis in shrimp aquaculture. The method is performed under isothermal conditions with a set of four specially designed primers that recognize six distinct sequences of the target. In the present study, according to the conservative regions of non-structural protein gene NS1, a set of four specific primers were designed, and a rapid detection of IHHNV was established by LAMP assay. The parameters of reaction time and temperature were optimized, and its specificity and sensitivity were assessed. The reactions were carried out at 60 degrees C, 62 degrees C, 63 degrees C, 64 degrees C, 65 degrees C, 66 degrees C, 67 degrees C, 68 degrees C for different time (0 min; 15 min; 30 min; 45 min; 60 min; 75 min). A plasmid pMDIHHNV carrying target sequence of LAMP detection was constructed. Ten-fold serially diluted pMDIHHNV (10(7)-10(0)copies/microL) was used as template for LAMP assay to investigate the detection limit. To determine the specificity, LAMP assays were carried out with DNA templates from other pathogens (White spot syndrome virus; WSSV, Taura Syndrome Virus; TSV, Aeromonas. hydrophila, V. alginolyticus, Vibrio. parahaemolytious, Escherichia. coli). The results showed the optimized LAMP assay for the rapid detection of IHHNV was performed at 65 degrees C for 60 min. The LAMP assay had an unequivocal detection limit of 100 copies/microL, and it was 1,000 times lower than that of PCR. The nucleic acids of other pathogens were not amplified by this LAMP system with the specific primers, which showed a good specificity. The resulting amplicons were detected using visual observation after the addition of SYBR Green I and gel electrophoresis. We investigated the efficacy of UNG (uracil-N-glycosylase) and dUTP in avoiding carry-over contamination in the LAMP assay procedure and explored its
Measles virus infection enhances IL-1 beta but reduces tumor necrosis factor-alpha expression in human monocytes.
Leopardi, R; Vainionpää, R; Hurme, M; Siljander, P; Salmi, A A
Monocytes may play a role in the immunologic abnormalities caused by measles. The effect of measles virus (MV) infection on peripheral blood monocyte functions is poorly known. We report that MV-infected PBM have an altered pattern of IL-1 beta and TNF-alpha production in response to stimulation with LPS and PMA in vitro. MV-infected peripheral blood monocytes produced higher amounts of IL-1 beta, whereas the production of TNF-alpha was reduced. The same effect was observed in the human monocytic cell line THP-1, which was used for RNA analysis. An increased steady-state level of IL-1 beta mRNA was observed in MV-infected cells, and the level of TNF-alpha mRNA was reduced. However, both IL-1 beta and TNF-alpha had about 50% increased transcription rate. Analysis of the mRNA stability after transcriptional block by actinomycin D showed that the TNF-alpha mRNA had a reduced half-life in MV-infected cells (about 30 vs 80 min in uninfected cells), whereas IL-1 beta mRNA stability was similar in uninfected and MV-infected cells. These results indicate that MV infection disturbs the immunoregulatory network by interfering with the monocyte functions. PMID:1527385
Herpes simplex virus type 1 hepatitis due to primary infection in a pancreas-kidney transplant recipient.
Feugeas, J; Mory, S; Jeulin, H; Velay, A; Pertek, J-P; Ladriere, M; Losser, M-R
Herpes simplex Virus (HSV) hepatitis is a rare complication of HSV-1 primary infection, with a delayed diagnosis, affecting mainly immunocompromised patients. We describe a case of HSV-1 hepatitis after primary infection occurring in the postoperative days after a pancreas-kidney transplantation. The patient presented with an unusual evolution of a persistent severe hepatitis associated with a persistent viremia (Quantitative Polymerase Chain Reaction) despite an adequate intravenous (iv) antiviral treatment. Abdominal computed tomography scan showed a miliary hepatitis. The diagnosis of HSV-1 hepatitis was confirmed by immuno-chemistry on liver biopsy. The donor was negative for anti-HSV antibodies, excluding contamination by the graft. This case report emphasizes a rather seldom risk of care-associated viral infections, predominantly in immunocompromised patients. PMID:27155056
Specificity of DNA vaccines against the U and M genogroups of infectious hematopoietic necrosis virus (IHNV) in rainbow trout (Oncorhynchus mykiss)
Penaranda, M.M.D.; LaPatra, S.E.; Kurath, G.
Infectious hematopoietic necrosis virus (IHNV) is a fish rhabdovirus that causes significant mortality in salmonid species. In North America IHNV has three major genogroups designated U, M, and L. Host-specificity of the M and U genogroups of IHNV has been established both in the field and in experimental challenges, with M isolates being more prevalent and more virulent in rainbow trout (Oncorhynchus mykiss), and U isolates being more prevalent and highly virulent in sockeye salmon (Oncorhynchus nerka). In this study, efficacy of DNA vaccines containing either M (pM) or U (pU) virus glycoprotein genes was investigated during intra- and cross-genogroup challenges in rainbow trout. In virus challenges at 7 days post-vaccination (early antiviral response), both pM and pU were highly protective against either M or U IHNV. In challenges at 28 days post-vaccination (specific antiviral response), both pM and pU were protective against M IHNV but the homologous pM vaccine was significantly more protective than pU in one of two experiments. At this stage both pM and pU induced comparably high protection against U IHNV challenge. Correlates of protection were also investigated by assessing the expression of the interferon-stimulated gene Mx-1 and the production of neutralizing antibodies (NAbs) following pM or pU DNA vaccination. Mx-1 gene expression, measured at 4 and 7 days post-vaccination as an indicator of the host innate immune response, was found to be significantly higher after pM than pU vaccination in some cases. Neutralizing antibody was produced in response to the two vaccines, but antibody titers did not show consistent correlation with protection. The results show that the rainbow trout innate and adaptive immune responses have some ability to distinguish between the U and M genogroup IHNV, but overall the pM and pU vaccines were protective against both homologous and cross-genogroup challenges.
Molecular characterization of E2 glycoprotein of classical swine fever virus: adaptation and propagation in porcine kidney cells.
Kumar, Rakesh; Barman, Nagendra N; Khatoon, Elina; Rajbongshi, Gitika; Deka, Nipu; Morla, Sudhir; Kumar, Sachin
Classical swine fever virus (CSFV) is the causative agent of a highly contagious disease, hog cholera in pigs. The disease is endemic in many parts of the world, and vaccination is the only way to protect the animals from CSFV infection. The lapinized vaccine strains are occasionally not protective because of animal to animal passage, inadequate vaccination strategy, suboptimal vaccine dose, and emergence of new variants. The surface glycoprotein E2 of CSFV is a major antigenic determinant and can modulate the disease outcome in pigs. In the present study, we characterized the CSFV in porcine kidney cells. The CSFV vaccine strains showed enhanced replication following 15 passages in porcine kidney cells. Nucleotide sequence analysis of the E2 protein gene of the cell culture-adapted vaccine strain of CSFV showed a mutation in putative amino acid sequences that are identical to its virulent counterpart. The study suggests the possibility of exaltation in vaccine strains following its adaptation in host cells and paves the way for a further exploration of the biology of its outbreak. PMID:25552311
Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity
Park, J.-W.; Moon, C.H.; Harmache, A.; Wargo, A.R.; Purcell, M.K.; Bremont, M.; Kurath, G.
Previously, we demonstrated that a representative M genogroup type strain of infectious haematopoietic necrosis virus (IHNV) from rainbow trout grows well in rainbow trout-derived RTG-2 cells, but a U genogroup type strain from sockeye salmon has restricted growth, associated with reduced genome replication and mRNA transcription. Here, we analysed further the mechanisms for this growth restriction of U-type IHNV in RTG-2 cells, using strategies that assessed differences in viral genes, host immune regulation and phosphorylation. To determine whether the viral glycoprotein (G) or non-virion (NV) protein was responsible for the growth restriction, four recombinant IHNV viruses were generated in which the G gene of an infectious IHNV clone was replaced by the G gene of U- or M-type IHNV and the NV gene was replaced by NV of U- or M-type IHNV. There was no significant difference in the growth of these recombinants in RTG-2 cells, indicating that G and NV proteins are not major factors responsible for the differential growth of the U- and M-type strains. Poly I:C pretreatment of RTG-2 cells suppressed the growth of both U- and M-type IHNV, although the M virus continued to replicate at a reduced level. Both viruses induced type 1 interferon (IFN1) and the IFN1 stimulated gene Mx1, but the expression levels in M-infected cells were significantly higher than in U-infected cells and an inhibitor of the IFN1-inducible protein kinase PKR, 2-aminopurine (2-AP), did not affect the growth of U- or M-type IHNV in RTG-2 cells. These data did not indicate a role for the IFN1 system in the restricted growth of U-type IHNV in RTG-2 cells. Prediction of kinase-specific phosphorylation sites in the viral phosphoprotein (P) using the NetPhosK program revealed differences between U- and M-type P genes at five phosphorylation sites. Pretreatment of RTG-2 cells with a PKC inhibitor or a p38MAPK inhibitor did not affect the growth of the U- and M-type viruses. However, 100 μm of the
[Renal ultrasound in fat necrosis].
Tizki, S; Lasry, F; Elftoiki, F Z; Hadj Khalifa, H; Itri, M; Khadir, K; Benchikhi, H
Subcutaneous fat necrosis is an uncommon disease that may be complicated with potentially fatal hypercalcemia or with nephrocalcinosis. We report on the case of a patient with a history of significant perinatal asphyxia, hospitalized for a urinary tract infection. Lesions of subcutaneous fat necrosis were noted, with asymptomatic hypercalcemia at 3.9mmol/L. A renal ultrasound was performed and showed echogenic medullary pyramids bilaterally, consistent with nephrocalcinosis and left nephrolithiasis. The treatment of hypercalcemia included hyperhydration, a diuretic and corticosteroids. Progression was characterized by the total regression of skin lesions and normalization of serum calcium. Hypercalcemia is a rare complication of subcutaneous fat necrosis. It develops within days to weeks after the appearance of skin lesions. Nephrocalcinosis appears after several weeks or months. Hypercalcemia must be treated in due time to avoid the impact on the kidney. PMID:23726682
Time Profile of Viral DNA in Aqueous Humor Samples of Patients Treated for Varicella-Zoster Virus Acute Retinal Necrosis by Use of Quantitative Real-Time PCR
Bernheim, D.; Germi, R.; Labetoulle, M.; Romanet, J. P.; Morand, P.
The objective of this study was to evaluate the kinetics of varicella-zoster virus (VZV) loads using quantitative PCR (qPCR) in patients treated for acute retinal necrosis (ARN). Six patients (52 ± 13 years old) with ARN syndrome were consecutively studied. Aqueous humor (AH) was sampled from both eyes of all patients for qPCR evaluation. The patients were treated with intravenous acyclovir and intravitreal injections of antiviral drugs. The mean follow-up time was 17.6 ± 16.4 months. Main outcome measures were the numbers of viral genome copies in the AH, assessed using real-time qPCR with hydrolysis probe technology with a threshold of detection of 200 copies/ml. Two main portions of the viral load curves were observed for each patient: a plateau phase (27.8 ± 24.9 days) and a decrease in the number of viral genome copies. The mean baseline viral load was 3.4 × 107 ± 4.45 × 107 copies/ml (6 × 106 to 1.2 × 108 copies/ml). The viral load decreased according to a logarithmic model, with a 50% reduction obtained in 3 ± 0.7 days. There was a significant viral load (>102 copies/ml) at 50 days after the onset of treatment, despite antiviral drugs. qPCR use demonstrated reproducible VZV DNA kinetics with a two-phase evolution: a plateau followed by a logarithmic decrease. These data suggest that high-dosage antiviral therapy administered for the conventional 10-day duration is insufficient for most patients. This series of patients responded with a similar decrease in viral load once treatment was initiated, and the data from these patients may be used to predict the responses of future patients. PMID:23637296
Human T-cell lymphotropic virus type 1-infected T lymphocytes impair catabolism and uptake of glutamate by astrocytes via Tax-1 and tumor necrosis factor alpha.
Szymocha, R; Akaoka, H; Dutuit, M; Malcus, C; Didier-Bazes, M; Belin, M F; Giraudon, P
Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of a chronic progressive myelopathy called tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In this disease, lesions of the central nervous system (CNS) are associated with perivascular infiltration by lymphocytes. We and others have hypothesized that these T lymphocytes infiltrating the CNS may play a prominent role in TSP/HAM. Here, we show that transient contact of human or rat astrocytes with T lymphocytes chronically infected by HTLV-1 impairs some of the major functions of brain astrocytes. Uptake of extracellular glutamate by astrocytes was significantly decreased after transient contact with infected T cells, while the expression of the glial transporters GLAST and GLT-1 was decreased. In two-compartment cultures avoiding direct cell-to-cell contact, similar results were obtained, suggesting possible involvement of soluble factors, such as cytokines and the viral protein Tax-1. Recombinant Tax-1 and tumor necrosis factor alpha (TNF-alpha) decreased glutamate uptake by astrocytes. Tax-1 probably acts by inducing TNF-alpha, as the effect of Tax-1 was abolished by anti-TNF-alpha antibody. The expression of glutamate-catabolizing enzymes in astrocytes was increased for glutamine synthetase and decreased for glutamate dehydrogenase, the magnitudes of these effects being correlated with the level of Tax-1 transcripts. In conclusion, Tax-1 and cytokines produced by HTLV-1-infected T cells impair the ability of astrocytes to manage the steady-state level of glutamate, which in turn may affect neuronal and oligodendrocytic functions and survival. PMID:10864655
Modulatory effect of CpG oligodeoxynucleotide on a DNA vaccine against nervous necrosis virus in orange-spotted grouper (Epinephelus coioides).
Chen, Shiang-Peng; Peng, Ran-Hong; Chiou, Pinwen P
We report the development of a DNA vaccine pcMGNNV2 against nervous necrosis virus (NNV), a leading cause of mass mortality in grouper larvae. In addition, the modulatory effect of CpG oligodeoxynucleotide (ODN), a Toll-like receptor 9 agonist, on the DNA vaccine was evaluated. The DNA vaccine alone elicited the production of NNV-specific antibodies, indicating that the vaccine was capable of triggering adaptive humoral response. Furthermore, significant induction of TLR9, Mx and IL-1β was observed in the spleen on day 7 post-vaccination, supporting that the vaccine could trigger TLR9 signaling. The incorporation of CpG ODN at high dose did not significantly affect the level of NNV-specific antibodies, but was able to moderately enhance the expression of Mx and IL-1β on day 7, indicating its ability in modulating innate response. After challenge with NNV, the vaccine alone enhanced the survival rate in infected larvae at both 1 and 2 weeks post-vaccination. The combination of CpG ODN further increased the survival rate at week 1 but not week 2. Interestingly, at week 2 the ODN appeared to induce a Th1-like response, as indicated by upregulation of T-bet (a Th1 marker) and downregulation of GATA-3 (a Th2 marker). Thus, the results suggest that the boosted Th1 response by CpG ODN does not augment the protection efficacy of pcMGNNV2 vaccine. To our best knowledge, this is the first report of a successful DNA vaccine against NNV in grouper. PMID:26093207
Time profile of viral DNA in aqueous humor samples of patients treated for varicella-zoster virus acute retinal necrosis by use of quantitative real-time PCR.
Bernheim, D; Germi, R; Labetoulle, M; Romanet, J P; Morand, P; Chiquet, C
The objective of this study was to evaluate the kinetics of varicella-zoster virus (VZV) loads using quantitative PCR (qPCR) in patients treated for acute retinal necrosis (ARN). Six patients (52 ± 13 years old) with ARN syndrome were consecutively studied. Aqueous humor (AH) was sampled from both eyes of all patients for qPCR evaluation. The patients were treated with intravenous acyclovir and intravitreal injections of antiviral drugs. The mean follow-up time was 17.6 ± 16.4 months. Main outcome measures were the numbers of viral genome copies in the AH, assessed using real-time qPCR with hydrolysis probe technology with a threshold of detection of 200 copies/ml. Two main portions of the viral load curves were observed for each patient: a plateau phase (27.8 ± 24.9 days) and a decrease in the number of viral genome copies. The mean baseline viral load was 3.4 × 10(7) ± 4.45 × 10(7) copies/ml (6 × 10(6) to 1.2 × 10(8) copies/ml). The viral load decreased according to a logarithmic model, with a 50% reduction obtained in 3 ± 0.7 days. There was a significant viral load (>102 copies/ml) at 50 days after the onset of treatment, despite antiviral drugs. qPCR use demonstrated reproducible VZV DNA kinetics with a two-phase evolution: a plateau followed by a logarithmic decrease. These data suggest that high-dosage antiviral therapy administered for the conventional 10-day duration is insufficient for most patients. This series of patients responded with a similar decrease in viral load once treatment was initiated, and the data from these patients may be used to predict the responses of future patients. PMID:23637296
Identification of a Rice stripe necrosis virus resistance locus and yield component QTLs using Oryza sativa × O. glaberrima introgression lines
Background Developing new population types based on interspecific introgressions has been suggested by several authors to facilitate the discovery of novel allelic sources for traits of agronomic importance. Chromosome segment substitution lines from interspecific crosses represent a powerful and useful genetic resource for QTL detection and breeding programs. Results We built a set of 64 chromosome segment substitution lines carrying contiguous chromosomal segments of African rice Oryza glaberrima MG12 (acc. IRGC103544) in the genetic background of Oryza sativa ssp. tropical japonica (cv. Caiapó). Well-distributed simple-sequence repeats markers were used to characterize the introgression events. Average size of the substituted chromosomal segments in the substitution lines was about 10 cM and covered the whole donor genome, except for small regions on chromosome 2 and 4. Proportions of recurrent and donor genome in the substitution lines were 87.59% and 7.64%, respectively. The remaining 4.78% corresponded to heterozygotes and missing data. Strong segregation distortion was found on chromosomes 3 and 6, indicating the presence of interspecific sterility genes. To illustrate the advantages and the power of quantitative trait loci (QTL) detection using substitution lines, a QTL detection was performed for scored traits. Transgressive segregation was observed for several traits measured in the population. Fourteen QTLs for plant height, tiller number per plant, panicle length, sterility percentage, 1000-grain weight and grain yield were located on chromosomes 1, 3, 4, 6 and 9. Furthermore, a highly significant QTL controlling resistance to the Rice stripe necrosis virus was located between SSR markers RM202-RM26406 (44.5-44.8 cM) on chromosome 11. Conclusions Development and phenotyping of CSSL libraries with entire genome coverage represents a useful strategy for QTL discovery. Mapping of the RSNV locus represents the first identification of a genetic factor
The pro-inflammatory cytokine tumor necrosis factor α stimulates expression of the carnitine transporter OCTN2 (novel organic cation transporter 2) and carnitine uptake via nuclear factor-κB in Madin-Darby bovine kidney cells.
Zhou, X; Ringseis, R; Wen, G; Eder, K
Carnitine uptake into tissues is mediated mainly by the novel organic cation transporter 2 (OCTN2), whose expression is upregulated in the liver of early-lactating dairy cows. It has been shown recently that pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), stimulate OCTN2 expression and carnitine uptake in intestinal cells and inflamed intestinal mucosa. Given that many early-lactating dairy cows show typical signs of hepatic and systemic inflammation, such as elevated concentrations of circulating TNFα and activation of the key regulator of inflammation, nuclear factor κB (NF-κB), in tissues, it is possible that upregulation of OCTN2 and increase of carnitine uptake by TNFα is mediated by NF-κB, a mechanism that might contribute to the upregulation of OCNT2 in the liver of early-lactating dairy cows. Thus, in the present study, we tested the hypothesis that TNFα stimulates OCTN2 gene expression and carnitine uptake via NF-κB in the bovine Madin-Darby bovine kidney (MDBK) cell line. Treatment with TNFα caused activation of NF-κB, increased the mRNA and protein concentration of OCTN2, and stimulated the uptake of carnitine in MDBK cells. In contrast, combined treatment of MDBK cells with TNFα and the NF-κB inhibitor BAY 11-7085 completely blocked the effect of TNFα on OCTN2 mRNA and protein concentration and uptake of carnitine. These findings suggest that the bovine OCTN2 gene and carnitine uptake are regulated by NF-κB. Future studies are required to show the in vivo relevance of this regulatory mechanism in cattle. PMID:25892691
BK and JC virus infections in healthy patients compared to kidney transplant recipients in Tunisia.
Boukoum, Hanen; Nahdi, Imen; Sahtout, Wissal; Skiri, Habib; Segondy, Michel; Aouni, Mahjoub
The human polyomaviruses BKPyV and JCPyV are members of Polyomaviridae family and after primary infections they persist as latent infection especially in the kidneys. BKVPy reactivation is mainly related to a renal nephropathy and JCV reactivation can induce the progressive multifocal leukoencephalopathy. The aim of this study was to investigate and to compare the presence of BKPyV and JCPyV in urine and plasma samples from immunocompromised and immunocompetent groups. The viral detection and quantification was done by a real time PCR from 100 healthy individuals and from 72 kidney transplanted patients (KTx) enrolled in a prospective study. Polyomavirus DNA urinary shedding was identified in 19% of healthy person, BKPyV in 6%; JCPyV more frequent in 13%. No individuals in this group developed polyomavirus viremia. BKPyV and JCPyV viruria was seen in 36% and 28% of KTx respectively, and 11% had a concomitant BKPyV and JCPyV viruria. Only BKPy viremia was detected in 5.5% of the KTx. In healthy persons, JCPyV shedding was associated with older individuals. However, in KTx, BKPyV was associated with younger age and male gender. No significant association was found between the patient's origin and BKPyV or JCPyV infection. In conclusion and consisting with previous reports, BKPyV and JCPyV prevalence and urinary loads were significantly higher in immunosuppressed compared to non-immunosuppressed individuals. In Addition and by contrast to KTx, JCPyV was more frequent than BKPyV in healthy individuals. Furthermore, the shedding of both polyomaviruses was differently associated with the age and the sex according to each population. PMID:27317859
Entry of Duck Hepatitis B Virus into Primary Duck Liver and Kidney Cells after Discovery of a Fusogenic Region within the Large Surface Protein▿
Maenz, Claudia; Chang, Shau-Feng; Iwanski, Alicja; Bruns, Michael
Hepatitis B viruses exhibit a narrow host range specificity that is believed to be mediated by a domain of the large surface protein, designated L. For duck hepatitis B virus, it has been shown that the pre-S domain of L binds to carboxypeptidase D, a cellular receptor present in many species on a wide variety of cell types. Nonetheless, only hepatocytes become infected. It has remained vague which viral features determine host range specificity and organotropicity. By using chymotrypsin to treat duck hepatitis B virus, we addressed the question of whether a putative fusogenic region within the amino-terminal end of the small surface protein may participate in viral entry and possibly constitute one of the determinants of the host range of the virus. Addition of the enzyme to virions resulted in increased infectivity. Remarkably, even remnants of enzyme-treated subviral particles proved to be inhibitory to infection. A noninfectious deletion mutant devoid of the binding region for carboxypeptidase D could be rendered infectious for primary duck hepatocytes by treatment with chymotrypsin. Although because of the protease treatment mutant and wild-type viruses may have become infectious in an unspecific and receptor-independent manner, their host range specificity was not affected, as shown by the inability of the virus to replicate in different hepatoma cell lines, as well as primary chicken hepatocytes. Instead, the organotropicity of the virus could be reduced, which was demonstrated by infection of primary duck kidney cells. PMID:17360753
Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus.
Kaplan, G; Totsuka, A; Thompson, P; Akatsuka, T; Moritsugu, Y; Feinstone, S M
Very little is known about the mechanism of cell entry of hepatitis A virus (HAV), and the identification of cellular receptors for this picornavirus has been elusive. Here we describe the molecular cloning of a cellular receptor for HAV using protective monoclonal antibodies raised against susceptible African green monkey kidney (AGMK) cells as probes. Monoclonal antibodies 190/4, 235/4 and 263/6, which reacted against similar epitopes, specifically protected AGMK cells against HAV infection by blocking the binding of HAV. Expression cloning and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the HAV cellular receptor 1 (HAVcr-1). Immunofluorescence analysis indicated that mouse Ltk- cells transfected with HAVcr-1 cDNA gained limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4. Our results demonstrate that the HAVcr-1 polypeptide is an attachment receptor for HAV and strongly suggest that it is also a functional receptor which mediates HAV infection. This report constitutes the first identification of a cellular receptor for HAV. Images PMID:8861957
Endogenous ADP-ribosylation of elongation factor 2 in polyoma virus-transformed baby hamster kidney cells
Fendrick, J.L.; Iglewski, W.J. )
Polyoma virus-transformed baby hamster kidney (pyBHK) cells were cultured in medium containing ({sup 32}P)orthophosphate and 105 (vol/vol) fetal bovine serum. A {sup 32}P-labeled protein with an apparent molecular mass of 97 kDa was immunoprecipitated from cell lysates with antiserum to ADP-ribosylated elongation factor 2 (EF-2). The {sup 32}P labeling of the protein was enhanced by culturing cells in medium containing 2% serum instead of 10% serum. The {sup 32}P label was completely removed from the protein by treatment with snake venom phosphodiesterase and the digestion product was identified as ({sup 32}P)AMP, indicating the protein was mono-ADP-ribosylated. HPLC analysis of tryptic peptides of the {sup 32}P-labeled 97-kDa protein and purified EF-2, which was ADP-ribosylated in vitro with diphtheria toxin fragment A and ({sup 32}P)NAD, demonstrated an identical labeled peptide in the two proteins. The data strongly suggest that EF-2 was endogenously ADP-ribosylated in pyBHK cells. Maximum incorporation of radioactivity in EF-2 occurred by 12 hr and remained constant over the subsequent 12 hr. It was estimated that 30-35% of the EF-2 was ADP-ribosylated in cells cultured in medium containing 2% serum. When {sup 32}P-labeled cultures were incubated in medium containing unlabeled phosphate, the {sup 32}P label was lost from the EF-2 within 30 min.
Persistent human immunodeficiency virus type 1 infection in human fetal glial cells reactivated by T-cell factor(s) or by the cytokines tumor necrosis factor alpha and interleukin-1 beta.
Tornatore, C; Nath, A; Amemiya, K; Major, E O
Human immunodeficiency virus type 1 (HIV-1) infection of the brain has been associated with a severe dementing illness in children and adults. However, HIV-1 antigens are most frequently found in macrophages and microglial cells. To determine the extent of susceptibility of neuroglial cells to infection, the HIV-1 genome was introduced into cells cultured from human fetal brain tissue. Astroglial cells rapidly transcribed the viral genome producing high levels of p24 protein and infectious virions which peaked two to three days posttransfection. Thereafter HIV-1 genome expression progressively diminished and a persistent phase of infection developed during which neither virus nor viral proteins could be demonstrated by immunodetection methods. Cocultivation with CD4+ T cells at any time during the persistent infection resulted in resumption of p24 synthesis and virus multiplication. The release of persistence did not require direct cell-cell contact between the glial and T cells, since separation of the two cell types across a permeable membrane resulted in a delayed but similar resumption of p24 synthesis and virus multiplication. The persistently infected glial cells could also be stimulated to produce viral p24 protein if either tumor necrosis factor alpha or interleukin-1 beta was added to the medium without T cells present. These results suggest that astrocytes may serve as an undetected reservoir for HIV-1 and disseminate the virus to other susceptible cells in the brain upon triggering by some cellular or biochemical signal. Images PMID:1920627
A hematopoietic virus disease of rainbow trout and sockeye salmon
Amend, Donald F.; Yasutake, William T.; Mead, Robert W.
A previously undescribed virus disease epizootic of hatchery rainbow trout (Salmo gairdneri) in British Columbia, Canada is presented. In the same locality, a similar virus disease was experienced among hatchery sockeye salmon (Oncorhynchus nerka). Typical symptoms included flashing, fecal casts, hemorrhagic areas at the base of fins, and petechial hemorrhages on the visceral fat and membranes in the abdominal cavity. Histopathologic changes were typified by extensive degeneration and necrosis in the hematopoietic tissues of the kidney and spleen. A virus was isolated from both species of fish on tissue culture and the viruses showed cross-infectivity. Based upon the pathological changes in the hematopoietic tissue and the demonstration of a vital infection, a tentative descriptive name was designated Infectious Hematopoietic Necrosis. The isolated viruses were distinctly different from the infectious pancreatic necrosis or viral hemorrhagic septicemia viruses of trout, but did show similarities to the Oregon sockeye and Sacramento River chinook viruses. Positive identification awaits further tests. The significance of these observations is the reporting of a new viral disease of rainbow trout and the extension of the geographic range of sockeye salmon viruses.
Prevalence and clinical and laboratory characteristics of kidney disease in anti-retroviral-naive human immunodeficiency virus-infected patients in South-South Nigeria.
Okafor, U H; Unuigbe, E I; Chukwuonye, E
Since the emergence of acquired immune deficiency syndrome (AIDS) about three decades ago, several renal disorders have been reported as common complications of human immunodeficiency virus (HIV) infection. These renal disorders result from diverse etiologies. The aim of this cross-sectional study was to determine the prevalence and clinical and laboratory characteristics of anti-retroviral-naοve HIV-infected patients with impaired kidney disorder in South-South Nigeria. This study was conducted on patients presenting at the University of Benin Teaching Hospital, Benin City in South-South Nigeria for six months. The patients' demographic data and clinical, hematological and biochemical parameters were assessed. Their glomerular filtration rate (GFR) was calculated and the protein excretion was assessed from the protein- creatinine ratio. Data were analyzed using statistical software program SPSS version 15.0. Three-hundred and eighty-three patients with a mean age of 35.39±8.78 years and a male: female ratio of 1:1 were studied; 53.3% had evidence of kidney disorder. The main clinical features in patients with kidney disorder were evidence of fluid retention, urinary symptoms, pallor and encephalopathy. The mean systolic and diastolic blood pressures were 115.33±17.17 and 72.33±14.31 mm Hg, respectively. The mean estimated GFR was 52.5 mL/min/1.73 m 2 . Patients with kidney disorder had higher proteinuria (P=0.001), lower mean CD4 cell count and packed cell volume (P=0.019 and 0.001, respectively). Kidney disorder is a common complication in HIV-infected patients, and they have clinical and laboratory anomalies. Screening of HIV/AIDS patients at the time of diagnosis will facilitate early diagnosis of kidney disorders in them. PMID:26787579
Identification of Optimal Donor-Recipient Combinations Among Human Immunodeficiency Virus (HIV)-Positive Kidney Transplant Recipients.
Locke, J E; Shelton, B A; Reed, R D; MacLennan, P A; Mehta, S; Sawinski, D; Segev, D L
For some patient subgroups, human immunodeficiency virus (HIV) infection has been associated with worse outcomes after kidney transplantation (KT); potentially modifiable factors may be responsible. The study goal was to identify factors that predict a higher risk of graft loss among HIV-positive KT recipients compared with a similar transplant among HIV-negative recipients. In this study, 82 762 deceased donor KT recipients (HIV positive: 526; HIV negative: 82 236) reported to the Scientific Registry of Transplant Recipients (SRTR) (2001-2013) were studied by interaction term analysis. Compared to HIV-negative recipients, the hepatitis C virus (HCV) amplified risk 2.72-fold among HIV-positive KT recipients (adjusted hazard ratio [aHR]: 2.72, 95% confidence interval [CI]: 1.75-4.22, p < 0.001). Forty-three percent of the excess risk was attributable to the interaction between HIV and HCV (attributable proportion of risk due to the interaction [AP]: 0.43, 95% CI: 0.23-0.63, p = 0.02). Among HIV-positive recipients with more than three HLA mismatches (MMs), risk was amplified 1.80-fold compared to HIV-negative (aHR: 1.80, 95% CI: 1.31-2.47, p < 0.001); 42% of the excess risk was attributable to the interaction between HIV and more than three HLA MMs (AP: 0.42, 95% CI: 0.24-0.60, p = 0.01). High-HIV-risk (HIV-positive/HCV-positive HLAwith more than three MMs) recipients had a 3.86-fold increased risk compared to low-HIV-risk (HIV-positive/HCV-negative HLA with three or fewer MMs)) recipients (aHR: 3.86, 95% CI: 2.37-6.30, p < 0.001). Avoidance of more than three HLA MMs in HIV-positive KT recipients, particularly among coinfected patients, may mitigate the increased risk of graft loss associated with HIV infection. PMID:27140837
Successful Eradication of Hepatitis C Virus by Interferon-Free Regimens in Two Patients with Advanced Liver Fibrosis following Kidney Transplantation
Sasaki, Reina; Kanda, Tatsuo; Yasui, Shin; Haga, Yuki; Nakamura, Masato; Yamato, Mutsumi; Wu, Shuang; Nakamoto, Shingo; Arai, Makoto; Mikami, Shigeru; Miyauchi, Hideaki; Matsubara, Hisahiro; Yokosuka, Osamu
Hepatitis C virus (HCV) infection leads to acute and chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Following kidney transplantation, HCV increases the risk of graft loss and patient mortality compared with uninfected patients. The achievement of a sustained virological response with antiviral therapy improves survival and diminishes the risk of hepatic decompensation in HCV patients after a kidney transplant. It has been reported that direct-acting antivirals (DAAs) are relatively safe and highly effective for the eradication of HCV in patients who are liver transplant recipients. In the present study, we investigated HCV eradication via interferon-free therapies with DAAs in two HCV patients with advanced liver fibrosis following renal transplantation. In both cases, the interferon-free regimens with DAAs were effective in eradicating HCV in the patients after kidney transplantation. No adverse events caused by interferon were identified with the exception of anemia. Interferon-free regimens with DAAs for recurrent HCV in patients following kidney transplantation are relatively safe and effective. However, attention should be focused on anemia during these treatments. PMID:27462193
... if You Have Kidney Disease Kidney Failure Expand Dialysis Kidney Transplant Preparing for Kidney Failure Treatment Choosing Not to Treat with Dialysis or Transplant Paying for Kidney Failure Treatment Contact ...
The coat protein of Alternanthera mosaic virus is the elicitor of a temperature-sensitive systemic necrosis in Nicotiana benthamiana, and interacts with a host boron transporter protein
Technology Transfer Automated Retrieval System (TEKTRAN)
Alternanthera mosaic virus (AltMV; Potexvirus) naturally infects several ornamental plants. Differences were previously noted between systemic symptoms induced in Nicotiana benthamiana by different isolates of AltMV, and by four infectious clones derived from AltMV-SP. Virus accumulation was enhance...
Application of isotope coded affinity tag (ICAT) analysis for the identification of differentially expressed proteins following infection of atlantic salmon (Salmo salar) with infectious hematopoietic necrosis virus (IHNV) or Renibacterium salmoninarum (BKD).
Booy, A T; Haddow, J D; Ohlund, L B; Hardie, D B; Olafson, R W
Aquaculture and commercial fisheries worldwide suffer from significant economic loss due to diseases of net-pen reared fish. In British Columbia, infectious hematopoietic necrosis (IHN) and bacterial kidney disease (BKD) epidemics occur because there are currently no commercially available drugs or fully licensed vaccines to treat these diseases. With a better understanding of the molecular mechanisms underlying these diseases, this circumstance might be significantly improved. In the present study, we have used a proteomics approach in an effort to identify and quantitate differentially expressed proteins in the liver and kidneys of diseased and healthy Atlantic salmon (Salmo salar). Isotope coded affinity tagging (ICAT), 2D gel electrophoresis, and multidimensional liquid chromatography coupled to tandem mass spectrometry (2D-LC MS/MS) were used to identify hundreds of differentially expressed proteins. While the direct significance of changes in expression levels of many proteins remains to be elucidated, others appear to be more clearly related to the infectious process. Examples of the latter are discussed here and include, a natural killer cell enhancement factor (NKEF), procathepsin L, superoxide-producing NADPH oxidase and interferon-induced viral resistance protein Mx (IFI-Mx). PMID:15822907
Association of Hepatitis C Virus Infection with Incidence and Progression of Chronic Kidney Disease in a Large Cohort of US Veterans
Molnar, Miklos Z; Alhourani, Hazem M; Wall, Barry M; Lu, Jun L; Streja, Elani; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P
Background An estimated 4 million Americans have been exposed to the hepatitis C virus (HCV) in the US population. The risk of incident and progressive chronic kidney disease and of mortality in patients with normal kidney function infected with HCV is unclear. Methods In a nationally representative cohort of 100,518 HCV+ and 920,531 HCV- US Veterans with normal baseline estimated glomerular filtration rate(eGFR), we examined the association of HCV infection with: (1)all-cause mortality, (2)incidence of decreased kidney function (defined as eGFR <60 ml/min/1.73m2 and 25% decrease in eGFR), (3)ESRD, and (4)rate of kidney function decline. Associations were examined in naïve and adjusted Cox models (for time-to-event analyses) and logistic regression models (for slopes), with sequential adjustments for important confounders. Propensity-matched cohort analysis was used in sensitivity analyses. Results The patients' age was 54.5±13.1(mean±SD) years, 22% were black and 92% male, and the baseline eGFR was 88±16 ml/min/1.73m2. In multivariate adjusted models HCV infection was associated with 2.2 fold higher mortality (fully adjusted hazard ratio(aHR), 95%CI: 2.17(2.13–2.21)), 15% higher incidence of decreased kidney function(aHR, 95%CI: 1.15(1.12–1.17)), 22% higher risk of steeper slopes of eGFR (adjusted odds ratio, 95%CI: 1.22(1.19–1.26)) and 98% higher hazard of ESRD (aHR, 95%CI: 1.98 (1.81–2.16)). Quantitatively similar results were found in propensity-matched cohort analyses. Conclusions HCV infection is associated with higher mortality risk, incidence of decreased kidney function and progressive loss of kidney function. Randomized controlled trials are warranted to determine whether treatment of HCV infection can prevent the development and progression of CKD and improve patient outcomes. PMID:25529816
Renal Papillary Necrosis: Role of Radiology
Pandya, Vaidehi K.
Renal Papillary Necrosis (RPN) is idefined as Ischemic necrobiosis of the papilla in the medulla of the kidneys. Variety of etiological factors are recognized which cause papillary necrosis, such as analgesic nephropathy, diabetes mellitus, urinary obstruction and sickle cell haemoglobinopathy. The early diagnosis of RPN is important to improve prognosis and reduce morbidity. Radiological Imaging offers early diagnosis and can guide prompt treatment of papillary necrosis and can minimize a decline in renal function. Here we report three cases of RPN with typical imaging findings. One of them was diabetic and hypertensive female with recurrent Urinary tract Infections and other was a male with no known co-morbidity. Both of them were diagnosed to have renal papillary necrosis on CT scan and were managed operatively and conservatively, respectively. Third case was a healthy female being investigated to be renal donor for her son. Here RPN was an incidental finding and was treated conservatively. Thus CT scan could detect it pre-operatively and complications due to transplantation of a kidney with papillary necrosis were avoided. So, we want to emphasize the importance of Radiology, particularly CT scanning in detection of RPN and to guide early and prompt treatment. PMID:26894147
... Home / Before The Transplant / Organ Facts / Kidney Organ Facts Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver ... Receiving "the call" About the Operation Heart Lung Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Kidney Facts The kidneys are a pair of reddish-brown ...
Clinical Manifestation of Self-Limiting Acute Retinal Necrosis
Brydak-Godowska, Joanna; Borkowski, Piotr; Szczepanik, Szymon; Moneta-Wielgoś, Joanna; Kęcik, Dariusz
Background The purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses. Material/Methods Ten patients (6F and 4M) aged 19–55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture. Results Peripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40–60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment – 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject. Conclusions A series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to
... fluid-filled sac. There are two types of kidney cysts. Polycystic kidney disease (PKD) runs in families. In PKD, the ... place of the normal tissue. They enlarge the kidneys and make them work poorly, leading to kidney ...
... Homework? Here's Help White House Lunch Recipes Your Kidneys KidsHealth > For Kids > Your Kidneys Print A A ... and it will be lighter. What Else Do Kidneys Do? Kidneys are always busy. Besides filtering the ...
... How Can I Help a Friend Who Cuts? Kidney Disease KidsHealth > For Teens > Kidney Disease Print A ... Syndrome Coping With Kidney Conditions What Do the Kidneys Do? You might never think much about some ...
... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...
... following early in life: blood-filtering treatments called dialysis a kidney transplant Children with dysplasia in only ... mild dysplasia of both kidneys may not need dialysis or a kidney transplant for several years. Kidney ...
... are two types of kidney cysts. Polycystic kidney disease (PKD) runs in families. In PKD, the cysts ... failure, dialysis or kidney transplants. Acquired cystic kidney disease (ACKD) usually happens in people who are on ...
Elevated Dengue Virus Nonstructural Protein 1 Serum Levels and Altered Toll-Like Receptor 4 Expression, Nitric Oxide, and Tumor Necrosis Factor Alpha Production in Dengue Hemorrhagic Fever Patients
Carvalho, Denise Maciel; Garcia, Fernanda Gonçalves; Terra, Ana Paula Sarreta; Lopes Tosta, Ana Cristina; Silva, Luciana de Almeida; Castellano, Lúcio Roberto; Silva Teixeira, David Nascimento
Background. During dengue virus (DV) infection, monocytes produce tumor necrosis factor alpha (TNF-α) and nitric oxide (NO) which might be critical to immunopathogenesis. Since intensity of DV replication may determine clinical outcomes, it is important to know the effects of viral nonstructural protein 1 (NS1) on innate immune parameters of infected patients. The present study investigates the relationships between dengue virus nonstructural protein 1 (NS1) serum levels and innate immune response (TLR4 expression and TNF-α/NO production) of DV infected patients presenting different clinical outcomes. Methodology/Principal Findings. We evaluated NO, NS1 serum levels (ELISA), TNF-α production by peripheral blood mononuclear cells (PBMCs), and TLR4 expression on CD14+ cells from 37 dengue patients and 20 healthy controls. Early in infection, increased expression of TLR4 in monocytes of patients with dengue fever (DF) was detected compared to patients with dengue hemorrhagic fever (DHF). Moreover, PBMCs of DHF patients showed higher NS1 and lower NO serum levels during the acute febrile phase and a reduced response to TLR4 stimulation by LPS (with a reduced TNF-α production) when compared to DF patients. Conclusions/Significance. During DV infection in humans, some innate immune parameters change, depending on the NS1 serum levels, and phase and severity of the disease which may contribute to development of different clinical outcomes. PMID:25580138
... is often caused by a lack of blood flow and oxygen to the kidney tissues (ischemia of the kidneys). ... treating conditions that can lead to decreased blood flow as well as decreased oxygen to the kidneys can reduce the risk for ...
Sunshine virus in Australian pythons.
Hyndman, Timothy H; Shilton, Cathy M; Doneley, Robert J T; Nicholls, Philip K
Sunshine virus is a recently discovered novel paramyxovirus that is associated with illness in snakes. It does not phylogenetically cluster within either of the two currently accepted paramyxoviral subfamilies. It is therefore only distantly related to the only other known genus of reptilian paramyxoviruses, Ferlavirus, which clusters within the Paramyxovirinae subfamily. Clinical and diagnostic aspects associated with Sunshine virus are as yet undescribed. The objective of this paper was to report the clinical presentation, virus isolation, PCR testing and pathology associated with Sunshine virus infection. Clinical records and samples from naturally occurring cases were obtained from two captive snake collections and the archives of a veterinary diagnostic laboratory. The clinical signs that are associated with Sunshine virus infection are localised to the neurorespiratory systems or are non-specific (e.g. lethargy, inappetence). Out of 15 snakes that were infected with Sunshine virus (detected in any organ by either virus isolation or PCR), the virus was isolated from four out of ten (4/10) sampled brains, 3/10 sampled lungs and 2/7 pooled samples of kidney and liver. In these same 15 snakes, PCR was able to successfully detect Sunshine virus in fresh-frozen brain (11/11), kidney (7/8), lung (8/11) and liver (5/8); and various formalin-fixed paraffin-embedded tissues (7/8). During a natural outbreak of Sunshine virus in a collection of 32 snakes, the virus could be detected in five out of 39 combined oral-cloacal swabs that were collected from 23 of these snakes over a 105 day period. All snakes that were infected with Sunshine virus were negative for reovirus and ferlavirus by PCR. Snakes infected with Sunshine virus reliably exhibited hindbrain white matter spongiosis and gliosis with extension to the surrounding grey matter and neuronal necrosis evident in severe cases. Five out of eight infected snakes also exhibited mild bronchointerstitial pneumonia
Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.
Suarez, J F; Rosa, R; Lorio, M A; Morris, M I; Abbo, L M; Simkins, J; Guerra, G; Roth, D; Kupin, W L; Mattiazzi, A; Ciancio, G; Chen, L J; Burke, G W; Goldstein, M J; Ruiz, P; Camargo, J F
In current practice, human immunodeficiency virus-infected (HIV(+) ) candidates with CD4 >200 cells/mm(3) are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm(3) among 38 anti-thymocyte globulin (ATG)-treated HIV-negative to HIV(+) kidney transplants performed at our center between 2006 and 2013. Median follow-up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm(3) ), however, was more common among patients with a baseline CD4 count 200-349 cells/mm(3) compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200-349 cells/mm(3) was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3-5.1) and 52 weeks (RR 14.3; 95% CI 2-100.4) after transplant. Patients with CD4 <200 cells/mm(3) at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log-rank p = 0.05). These findings suggest that ATG must be used with caution in HIV(+) kidney allograft recipients with a pretransplant CD4 count <350 cells/mm(3) . PMID:26953224
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Virus-Specific CD8(+) T Cells Cross-Reactive to Donor-Alloantigen Are Transiently Present in the Circulation of Kidney Transplant Recipients Infected With CMV and/or EBV.
Heutinck, K M; Yong, S L; Tonneijck, L; van den Heuvel, H; van der Weerd, N C; van der Pant, K A M I; Bemelman, F J; Claas, F H J; Ten Berge, I J M
T cells play a dual role in transplantation: They mediate transplant rejection and are crucial for virus control. Memory T cells generated in response to pathogens can cross-react to alloantigen, a phenomenon called heterologous immunity. Virus-specific CD8(+) T cells cross-reacting to donor-alloantigen might affect alloimmune responses and hamper tolerance induction following transplantation. Here, we longitudinally studied these cross-reactive cells in peripheral blood of 25 kidney transplant recipients with a cytomegalovirus and/or Epstein-Barr virus infection. Cross-reactive T cells were identified by flow cytometry as virus-specific T cells that proliferate in response to donor cells in a mixed-lymphocyte reaction. In 13 of 25 patients, we found cross-reactivity to donor cells for at least 1 viral epitope before (n = 7) and/or after transplantation (n = 8). Cross-reactive T cells were transiently present in the circulation, and their precursor frequency did not increase following transplantation or viral infection. Cross-reactive T cells expressed interferon-γ and CD107a in response to both alloantigen and viral peptide and resembled virus-specific T cells in phenotype and function. Their presence was not associated with impaired renal function, proteinuria, or rejection. In conclusion, virus-specific T cells that cross-react to donor-alloantigen are transiently detectable in the circulation of kidney transplant recipients. PMID:26603974
... our e-newsletter! Aging & Health A to Z Kidney Problems Basic Facts & Information The kidneys are two ... the production of red blood cells. What are Kidney Diseases? For about one-third of older people, ...
... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You have a higher risk of kidney disease if you have diabetes, high blood pressure, or ...
... taking out waste products and making urine. Kidney tests check to see how well your kidneys are working. They include blood, urine, and imaging tests. Early kidney disease usually does not have signs ...
... until you go to the bathroom. Most kidney diseases attack the nephrons. This damage may leave kidneys ... medicines. You are at greater risk for kidney disease if you have diabetes, high blood pressure, or ...
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... urine exits the kidney and enters the ureter. As urine can become very concentrated as it passes through the kidneys. When the urine ... chemicals dissolved in the urine can crystallize, forming a kidney stone (renal calculus). Usually the calculus is ...
... enough red blood cells. This is called kidney failure. If your kidneys fail, you need treatment to ... providers, family, and friends, most people with kidney failure can lead full and active lives. NIH: National ...
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[Programmed necrosis: a new target for ischemia reperfusion injury].
Li, Xiaojing; Ming, Yingzi; Niu, Ying; Liu, Qianwen; Ye, Qifa
Recent years, the researchers have found a new type of cell death, referred to programmed necrosis or necroptosis, which involves the death receptor and the ligand binds and is initiated under the inhibition of apoptosis pathway. Programmed necrosis possesses the morphological features of typical necrosis accompanied by inflammation. The receptor interacting protein kinase 1/3(RIPK1/3) can be inhibited by the specific inhibitors, such as necrostatin-1. RIPK1/3 could regulate programmed necrosis and play a key role in the process. The significance of programmed necrosis in ischemia-reperfusion injury (IRI) has been attracted great attention at present. Simultaneously, a series of studies have found it also involves in the IRI of heart, kidney, brain and retina. PMID:27592584
Differential immune gene expression profiles in susceptible and resistant full-sibling families of Atlantic salmon (Salmo salar) challenged with infectious pancreatic necrosis virus (IPNV).
Reyes-López, Felipe E; Romeo, Jose S; Vallejos-Vidal, Eva; Reyes-Cerpa, Sebastián; Sandino, Ana M; Tort, Lluis; Mackenzie, Simon; Imarai, Mónica
This study aims to identify at the expression level the immune-related genes associated with IPN-susceptible and resistant phenotypes in Atlantic salmon full-sibling families. We have analyzed thirty full-sibling families infected by immersion with IPNV and then classified as resistant or susceptible using a multivariate survival analysis based on a gamma-Cox frailty model and the Kaplan-Meier mortality curves. In four families within each group head kidneys were pooled for real-time PCR and one-color salmon-specific oligonucleotide microarray (21K) analysis at day 1 and 5 post-infection. Transcripts involved in innate response (IL-6, IFN-α), antigen presentation (HSP-70, HSP-90, MHC-I), TH1 response (IL-12, IFN-γ, CRFB6), immunosuppression (IL-10, TGF-β1) and leukocyte activation and migration (CCL-19, CD18) showed a differential expression pattern between both phenotypes, except in IL-6. In susceptible families, except for IFN-γ, the expressions dropped to basal values at day 5 post-infection. In resistant families, unlike susceptible families, levels remained high or increased (except for IL-6) at day 5. Transcriptomic analysis showed that both families have a clear differential expression pattern, resulting in a marked down-regulation in immune related genes involved in innate response, complement system, antigen recognition and activation of immune response in IPN-resistant. Down-regulation of genes, mainly related to tissue differentiation and protein degradation metabolism, was also observed in resistant families. We have identified an immune-related gene patterns associated with susceptibility and resistance to IPNV infection of Atlantic salmon. This suggests that a limited immune response is associated with resistant fish phenotype to IPNV challenge while a highly inflammatory but short response is associated with susceptibility. PMID:26123889
Viral nervous necrosis virus persistently replicates in the central nervous system of asymptomatic gilthead seabream and promotes a transient inflammatory response followed by the infiltration of IgM+ B lymphocytes.
López-Muñoz, Azucena; Sepulcre, María P; García-Moreno, Diana; Fuentes, Inmaculada; Béjar, Julia; Manchado, Manuel; Álvarez, M Carmen; Meseguer, José; Mulero, Victoriano
The viral nervous necrosis virus (VNNV) is the causal agent of viral encephalopathy and retinopathy (VER), a worldwide fish disease that is responsible for high mortality in both marine and freshwater species. Infected fish suffer from encephalitis, which leads to abnormal swimming behavior and extensive cellular vacuolation and neuronal degeneration in the central nervous system (CNS) and retina. The marine fish gilthead seabream (Sparus aurata) does not develop VER but it is an asymptomatic carrier of VNNV. In this study, we report that VNNV was able to replicate and persist for up to 3 months in the CNS of the gilthead seabream without causing any neural damage. In addition, we found an early inflammatory response in the CNS that was characterized by the induction of genes encoding pro-inflammatory cytokines, a delayed but persistent induction of anti-inflammatory cytokines, and the infiltration of IgM(+) B lymphocytes, suggesting that local adaptive immunity played a major role in the control of VNNV in the CNS of this species. PMID:22402274
... renal papillary necrosis, especially after taking over-the-counter pain medicines ... diabetes or sickle cell anemia may reduce your risk. To prevent renal ... over-the-counter pain relievers. Do not take more than the ...
Acute Systemic Infection with Dengue Virus Leads to Vascular Leakage and Death through Tumor Necrosis Factor-α and Tie2/Angiopoietin Signaling in Mice Lacking Type I and II Interferon Receptors
Limkittikul, Kriengsak; Sakai, Yusuke; Takakura, Nobuyuki; Saijo, Masayuki
Severe dengue is caused by host responses to viral infection, but the pathogenesis remains unknown. This is, in part, due to the lack of suitable animal models. Here, we report a non-mouse-adapted low-passage DENV-3 clinical isolate, DV3P12/08, derived from recently infected patients. DV3P12/08 caused a lethal systemic infection in type I and II IFN receptor KO mice (IFN-α/β/γR KO mice), which have the C57/BL6 background. Infection with DV3P12/08 induced a cytokine storm, resulting in severe vascular leakage (mainly in the liver, kidney and intestine) and organ damage, leading to extensive hemorrhage and rapid death. DV3P12/08 infection triggered the release of large amounts of TNF-α, IL-6, and MCP-1. Treatment with a neutralizing anti-TNF-α antibody (Ab) extended survival and reduced liver damage without affecting virus production. Anti-IL-6 neutralizing Ab partly prolonged mouse survival. The anti-TNF-α Ab suppressed IL-6, MCP-1, and IFN-γ levels, suggesting that the severe response to infection was triggered by TNF-α. High levels of TNF-α mRNA were expressed in the liver and kidneys, but not in the small intestine, of infected mice. Conversely, high levels of IL-6 mRNA were expressed in the intestine. Importantly, treatment with Angiopoietin-1, which is known to stabilize blood vessels, prolonged the survival of DV3P12/08-infected mice. Taken together, the results suggest that an increased level of TNF-α together with concomitant upregulation of Tie2/Angiopoietin signaling have critical roles in severe dengue infection. PMID:26844767
Preclinical safety evaluation of recombinant adeno-associated virus 2 vector encoding human tumor necrosis factor receptor-immunoglobulin Fc fusion gene.
Zhou, Xiaobing; Shen, Lianzhong; Liu, Li; Wang, Chao; Qi, Weihong; Zhao, Aizhi; Wu, Xiaobing; Li, Bo
Recombinant adeno-associated virus (rAAV) 2 vector gene therapy offers promise for the healing of Rheumatoid arthritis. To support the clinical development of the candidate gene therapeutic product in China, a comprehensive preclinical safety assessment of rAAV2 encoding human TNF receptor-immunoglobulin Fc fusion gene (rAAV2/human TNFR:Fc), were conducted in 3 species of experimental animals. No abnormal findings were observed in mice following single intravenous administration with test article. Compared with the control group, no differences in mean body weight, food consumption in rats and monkeys following the repeated intraarticular administration with rAAV2/human TNFR:Fc. There were also no significant adverse effects due to treatment noted by clinical chemistry, hematology and pathology assessments. After intraarticular administration with rAAV2/human TNFR:Fc, the vector DNA initially distributed to spleen, lymph nodes, and joint synovium. The vector DNA cleared rapidly as it could be detected mainly at the site of injection by 91 d post-administration (182 d for monkey). Taken together, localized delivery of rAAV2/human TNFR:Fc showed no significant toxicity in mice, rats, and monkeys, which support the planned clinical evaluation of this product. PMID:26837862
Productive replication of nephropathogenic infectious bronchitis virus in peripheral blood monocytic cells, a strategy for viral dissemination and kidney infection in chickens.
Reddy, Vishwanatha R A P; Trus, Ivan; Desmarets, Lowiese M B; Li, Yewei; Theuns, Sebastiaan; Nauwynck, Hans J
In the present study, the replication kinetics of nephropathogenic (B1648) and respiratory (Massachusetts-M41) IBV strains were compared in vitro in respiratory mucosa explants and blood monocytes (KUL01(+) cells), and in vivo in chickens to understand why some IBV strains have a kidney tropism. B1648 was replicating somewhat better than M41 in the epithelium of the respiratory mucosa explants and used more KUL01(+) cells to penetrate the deeper layers of the respiratory tract. B1648 was productively replicating in KUL01(+) monocytic cells in contrast with M41. In B1648 inoculated animals, 10(2.7-6.8) viral RNA copies/100 mg were detected in tracheal secretions at 2, 4, 6, 8, 10 and 12 days post inoculation (dpi), 10(2.4-4.5) viral RNA copies/mL in plasma at 2, 4, 6, 8, 10 and 12 dpi and 10(1.8-4.4) viral RNA copies/10(6) mononuclear cells in blood at 2, 4, 6 and 8 dpi. In M41 inoculated animals, 10(2.6-7.0) viral RNA copies/100 mg were detected in tracheal secretions at 2, 4, 6, 8 and 10 dpi, but viral RNA was not demonstrated in plasma and mononuclear cells (except in one chicken at 6 dpi). Infectious virus was detected only in plasma and mononuclear cells of the B1648 group. At euthanasia (12 dpi), viral RNA and antigen positive cells were detected in lungs, liver, spleen and kidneys of only the B1648 group and in tracheas of both the B1648 and M41 group. In conclusion, only B1648 can easily disseminate to internal organs via a cell-free and -associated viremia with KUL01(+) cells as important carrier cells. PMID:27412035
... Institute, Inc., Kidney School National Kidney Foundation MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... Organizations . (PDF, 345 KB) Alternate Language URL Solitary Kidney Page Content On this page: What is a ...
Horseshoe kidney transplantation
Kanyári, Zsolt; Zádori, Gergely; Zsom, Lajos; Berhés, Mariann; Hamar, Mátyás; Kóbor, Krisztina; Péter, Antal
Horseshoe kidney is a fusion anomaly found in approximately one in 400–600 people. Due to vascular and ureteral variations, transplantation with a horseshoe kidney presents a technical challenge. In our case, the isthmus connected the upper poles and contained parenchyma. It consisted of three renal arteries, five veins collected to the inferior vena cava, and two ureters and pyelons. It was implanted en bloc to the left side retroperitoneally. During the early period, cellular and humoral rejection was confirmed and treated. For a urine leak, double J catheters were implanted into both ureters. Later, the first catheter was removed. Subsequently, urinary sepsis developed, necessitating graftectomy. The uncommon anatomy of ureters and antibody-mediated rejection (AMR) may both be factors for a ureter tip necrosis led to an infected urinoma. After other Hungarian authors, we also report a horseshoe kidney transplantation that was technically successful. However, after an adequately treated but severe acute humoral rejection, the patient developed sepsis, and the kidney had to be removed. We conclude that transplantation with horseshoe kidney is technically feasible but may increase the risk for urinary complications and resultant infections. Careful consideration of risk and benefit is advised when a transplant professional is faced with this option. PMID:26120481
Phenotypic change from transformed to normal induced by benzoquinonoid ansamycins accompanies inactivation of p60src in rat kidney cells infected with Rous sarcoma virus.
Uehara, Y; Hori, M; Takeuchi, T; Umezawa, H
Three benzenoid ansamycin antibiotics (herbimycin, macbecin, and geldanamycin) were found to reduce the intracellular phosphorylation of p60src at a permissive temperature (33 degrees C) in a rat kidney cell line infected with a temperature-sensitive mutant of Rous sarcoma virus. This effect was accompanied by morphological changes from the transformed to the normal phenotype. The filamentous staining pattern of actin fibers was observed in the cells treated with these antibiotics at 33 degrees C. Removal of the antibiotics allowed the cells to revert to the transformed morphology. Ansamitocin, another benzenoid ansamycin, and naphthalenoid ansamycins such as streptovaricin and rifamycins did not show this effect. Pulse-labeling of the antibiotic-treated cultures with 32Pi showed a marked reduction of 32P radioactivity incorporated into p60src. A parallel experiment with [35S]methionine showed that synthesis of p60src was slightly inhibited. The immune complex prepared by mixing the herbimycin-treated cell extracts with antibody against p60src was inactive in vitro in phosphorylating the complex itself. On the contrary, the immune complex derived from untreated cells was active in vitro even in the presence of the antibiotics. These results suggest that benzoquinonoid ansamycins have no direct effect on src kinase but destroy its intracellular environment, resulting in an irreversible alteration of p60src and loss of catalytic activity. Images PMID:3023921
Comparison of diploid fibroblast and rabbit kidney tissue cultures and a diploid fibroblast microtiter plate system for the isolation of herpes simplex virus.
Langenberg, A; Zbanyszek, R; Dragavon, J; Ashley, R; Corey, L
We evaluated the relative sensitivities of two cell systems (rabbit kidney [RK] and human diploid fibroblast [DF; human embryonic tonsil]) in standard tube cultures versus DF cells in a 48-well microtiter plate system for the detection of both symptomatic and asymptomatic herpes simplex virus (HSV) infection. At least one system isolated HSV in 111 of 809 specimens (13.7%). HSV was isolated in RK tube cultures from 110 specimens (99%), in DF tube cultures from 91 specimens (82%), and in DF microtiter plates from 95 specimens (86%). The frequency of HSV isolation varied with the anatomic site and the presence or absence of a herpetic lesion. The sensitivities of the three culture systems remained similar whether the specimens were obtained from lesions or whether the specimens were taken to determine if asymptomatic excretion of HSV was present. While RK tube cultures were more sensitive than DF tube cultures, the DF microtiter plate system was as sensitive as DF tube cultures and its use is supported as a cheaper and less labor-intensive method for the detection of HSV. PMID:2846647
Epstein-Barr Virus (EBV) Latent Membrane Protein-1 Down-Regulates Tumor Necrosis Factor-α (TNF-α) Receptor-1 and Confers Resistance to TNF-α-Induced Apoptosis in T Cells
Chuang, Huai-Chia; Lay, Jong-Ding; Chuang, Shuang-En; Hsieh, Wen-Chuan; Chang, Yao; Su, Ih-Jen
The infection of T cells by Epstein-Barr virus (EBV) may result in hemophagocytic syndrome (HPS) through enhanced cytokine secretion, particularly tumor necrosis factor-α (TNF-α), by EBV latent membrane protein-1 (LMP-1). One bewildering observation of HPS patients is relapsing disease or progression to T-cell lymphoma. This finding raises the question whether EBV LMP-1-expressing T cells may survive and proliferate in the cytokine milieu of HPS. To explore this possibility, we tested the sensitivity of LMP-1-expressing T cells to apoptosis in the presence of TNF-α. LMP-1 up-regulated TNF-α through TRAF2,5 and nuclear factor-κB pathway in T cells. The LMP-1-expressing T cells then became resistant to TNF-α-induced apoptosis. Interestingly, the expression of TNFR1 was remarkably down-regulated by LMP-1 in T cells. Furthermore, the TNF-α/TNFR1 downstream death signal TNFR1-associated death domain protein was constitutively recruited by LMP-1, and the activities of apoptotic caspases 3, 8, and 9 were suppressed. Reconstitution of TNFR1 successfully reversed the TNF-α-induced apoptotic cascades. Therefore, EBV LMP-1 not only activates T cells to proliferate but also confers resistance to TNF-α-mediated apoptosis via down-regulation of TNFR1 in the cytokine milieu of HPS. This finding provides a potential mechanism to explain the disease persistence or progression to T-cell lymphoma in HPS patients. PMID:17456766
Herpes Simplex Virus 1 E3 Ubiquitin Ligase ICP0 Protein Inhibits Tumor Necrosis Factor Alpha-Induced NF-κB Activation by Interacting with p65/RelA and p50/NF-κB1
Zhang, Jie; Wang, Kezhen
NF-κB plays central roles in regulation of diverse biological processes, including innate and adaptive immunity and inflammation. HSV-1 is the archetypal member of the alphaherpesviruses, with a large genome encoding over 80 viral proteins, many of which are involved in virus-host interactions and show immune modulatory capabilities. In this study, we demonstrated that the HSV-1 ICP0 protein, a viral E3 ubiquitin ligase, was shown to significantly suppress tumor necrosis factor alpha (TNF-α)-mediated NF-κB activation. ICP0 was demonstrated to bind to the NF-κB subunits p65 and p50 by coimmunoprecipitation analysis. ICP0 bound to the Rel homology domain (RHD) of p65. Fluorescence microscopy demonstrated that ICP0 abolished nuclear translocation of p65 upon TNF-α stimulation. Also, ICP0 degraded p50 via its E3 ubiquitin ligase activity. The RING finger (RF) domain mutant ICP0 (ICP0-RF) lost its ability to inhibit TNF-α-mediated NF-κB activation and p65 nuclear translocation and degrade p50. Notably, the RF domain of ICP0 was sufficient to interact with p50 and abolish NF-κB reporter gene activity. Here, it is for the first time shown that HSV-1 ICP0 interacts with p65 and p50, degrades p50 through the ubiquitin-proteasome pathway, and prevents NF-κB-dependent gene expression, which may contribute to immune evasion and pathogenesis of HSV-1. PMID:24067962
Cytoarchitecture of Kirsten sarcoma virus-transformed rat kidney fibroblasts: butyrate-induced reorganization within the actin microfilament network.
Ryan, M P; Higgins, P J
Murine sarcoma virus-transformed rat fibroblasts (KNRK cells) undergo marked cytoarchitectural reorganization during in vitro exposure to sodium-n-butyrate (NaB) resulting in restoration of (1) a more typical fibroblastoid morphology, (2) proper cell-to-cell orientation, and (3) substratum adherence. Augmented cell spreading, involving greater than 90% of the population, was a function of culture density and time of exposure to NaB (2 mM final concentration). Induced cell spreading reflected a 2.5- to 3.0-fold increase in both total cellular actin content and deposition of actin into the detergent-resistant cytoskeleton. Cytoskeletal actin deposition in response to NaB was accompanied by the formation of occasionally dense, parallel alignments of F-actin-containing microfilaments and by a dramatic increase in the size and incidence of actin-enriched membrane ruffles. Long-term NaB-treated cells exhibited parallel orientations of microfilaments similar to those found in untransformed fibroblasts. Increased cytoskeletal actin occurred within 24 hr of NaB exposure, correlating with the initial reorganization of actin-containing microfilaments detected microscopically, and reflected concomitant 3-fold increases in cellular alpha-actinin and fibronectin content. In contrast, the amount of vimentin, tropomyosin, and tubulin in NaB-treated cells was significantly decreased. NaB-induced morphologic restructuring of sarcoma virus-transformed fibroblasts, thus, impacts on all three basic cytoskeletal systems. Selective increases, however, were evident in particular cytoskeletal proteins (actin, alpha-actinin, fibronectin) implicated in microfilament networking and cell spreading. PMID:2844835
Subcutaneous encapsulated fat necrosis.
Aydin, Dogu; Berg, Jais O
We have described subcutaneous encapsulated fat necrosis, which is benign, usually asymptomatic and underreported. Images have only been published on two earlier occasions, in which the necrotic nodules appear "pearly" than the cloudy yellow surface in present case. The presented image may help future surgeons to establish the diagnosis peroperatively. PMID:27099753
Healthy kidneys clean your blood by removing excess fluid, minerals, and wastes. They also make hormones that keep your ... strong and your blood healthy. But if the kidneys are damaged, they don't work properly. Harmful ...
... right diagnosis. [ Top ] What should a person do days before a kidney biopsy? Days before the procedure, ... Top ] What can a person expect on the day of the kidney biopsy? A person should arrive ...
... the surgical cut is located. Recovery after a laparoscopic procedure is most often quicker, with less pain. Outlook (Prognosis) The outcome is most often good when a single kidney is removed. If both kidneys are removed, ...
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... cortex to the inner medulla. The renal pelvis is the funnel through which urine exits the kidney ... a kidney stone (renal calculus). Usually the calculus is the size of a small pebble. But ureters ...
... of the spine. Every minute, a person's kidneys filter about 3 ounces of blood, removing wastes and ... occur. As a result, the kidney can't filter wastes and extra water from the blood. One ...
... infections Side effects from medicines used to prevent transplant rejection Loss of transplanted kidney ... tries to destroy it. In order to avoid rejection, almost all kidney transplant recipients must take medicines that suppress their immune ...
... Dimes National Kidney Foundation Urology Care Foundation MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... Disease Organizations . (PDF, 345 KB) Alternate Language URL Kidney Dysplasia Page Content On this page: What is ...
Anti-hepatitis B virus effect of matrine-type alkaloid and involvement of p38 mitogen-activated protein kinase and tumor necrosis factor receptor-associated factor 6.
Chen, Jia-Xin; Shen, Hong-Hui; Niu, Ming; Guo, Yu-Ming; Liu, Xiao-Qiong; Han, Yan-Zhong; Zhang, Ya-Ming; Zhao, Yan-Ling; Bai, Bing-Ke; Zhou, Wen-Jun; Xiao, Xiao-He
The matrine-type alkaloid, oxymatrine inhibits hepatitis B virus (HBV) replication but very little is known about these effects in other matrine-type alkaloids, including sophoridine and sophocarpine. Therefore, we compared the in vitro anti-HBV effects of matrine, oxymatrine, sophocarpine, and sophoridine by treating an HBV-transfected cell line (HepG2.2.15) with 0.4-1.6mM of the compounds for 24 or 72h. The levels of the HBV surface antigen (HBsAg) and e antigen (HBeAg) in the culture medium, as well as the intracellular and extracellular HBV DNA levels, were determined. Metabolomic analysis and detection of the mRNA level of p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor receptor-associated factor (TRAF) 6, extracellular signal-regulated kinase (ERK) 1, NOD-like receptor family pyrin domain containing 10 (NLRP10), and caspase-1 were conducted in sophoridine-treated HepG2.2.15 cells. HepG2.2.15 cell exposure to 0.4-1.6mM sophocarpine or sophoridine for 24h reduced the HBsAg level of the medium more effectively than exposure to matrine and oxymatrine did, and reduced the HBeAg levels more effectively than these compounds did at 1.6mM. Sophoridine (0.4-1.6mM) reduced the cell medium HBV DNA levels more than the same concentrations of matrine, oxymatrine, or sophocarpine did. After 72h, 0.4 and 0.8mM sophoridine reduced HBsAg and intracellular HBV DNA levels more potently than matrine, oxymatrine, or sophocarpine did. Furthermore, sophoridine (0.8mM) potently reduced the cell medium HBeAg levels while the metabolomic analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine for 72h exhibited reduced cycloleucine and phytosphingosine levels. In addition, the mRNA expression analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine showed reduced levels of p38 MAPK, TRAF6, ERK1, NLRP10, and caspase-1. Sophoridine produced more potent anti-HBV effects than matrine, oxymatrine, and sophocarpine did. These effects may be related
... ago. Kidney Disease About your kidneys About your kidneys Your kidneys are vital organs that remove waste ... long as possible. Kidney-friendly diet for CKD Kidney-friendly diet You may be able to prevent ...
... FOR KIDNEY DISEASE? HIV MEDICATIONS AND THE KIDNEYS DIALYSIS AND KIDNEY TRANSPLANTATION THE BOTTOM LINE WHY SHOULD ... disease (ESRD) or kidney failure. This can require dialysis or a kidney transplant. The rate of kidney ...
Pyelo-ureteral necrosis after renal transplantation.
Spasovski, Goce B; Masin-Spasovska, Jelka; Stavridis, Sotir; Saiti, Skender; Lekovski, Ljupco
Because of the limited chance of receiving a kidney transplant (for several well-known reasons), a lot of desperate dialysis patients procure an unrelated donor kidney transplant against all medical advice. This type of renal paid transplantation is associated with many surgical complications and invasive opportunistic infections that increase the morbidity and mortality in this group of transplant recipients. In this report, we describe a case of a 22-year-old girl with a segmental infarction of the graft lower pole and a complete pyelo-ureteral necrosis as a consequence of some vascular damage, complicated by a pathohistological finding of an invasive candidiasis. Despite the successful surgical pyelovesical anastomosis and the good recovery of the patient and the kidney, long-term prognosis remains poor. The lack of information from the transplanting center regarding both donor and recipient and the associated, unacceptable risks on the graft and patient survival in unrelated, paid transplant recipients reinforce the standpoint that this practice should be abandoned. PMID:18204913
Technology Transfer Automated Retrieval System (TEKTRAN)
Lytic bacteriophages, viruses which infect and lyse bacterial cells, can provide a natural method to reduce bacterial pathogens on produce commodities. The use of multi-phage cocktails is most likely to be effective against bacterial pathogens on produce commodities, and minimize the development of...
... Goodpasture syndrome IgA nephropathy Interstitial nephritis Lupus nephritis Medullary cystic kidney disease Membranoproliferative glomerulonephritis Membranous nephropathy Minimal change disease Nephrotic ...
You have two kidneys. They are fist-sized organs on either side of your backbone above your waist. The tubes inside filter and ... blood, taking out waste products and making urine. Kidney cancer forms in the lining of tiny tubes ...
... be signs of kidney stones that need a doctor's help: Extreme pain in your back or side that will not go away Blood in your urine Fever and chills Vomiting Urine that smells bad or looks cloudy A burning feeling when you urinate Your doctor will diagnose a kidney stone with urine, blood, ...
... Human Development March of Dimes National Office MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... Organizations . (PDF, 345 KB) Alternate Language URL Ectopic Kidney Page Content On this page: What is an ...
Emerging concepts in the management of acute retinal necrosis.
Wong, Robert William; Jumper, J Michael; McDonald, H Richard; Johnson, Robert N; Fu, Arthur; Lujan, Brandon J; Cunningham, Emmett T
Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition. PMID:23235944
... Homework? Here's Help White House Lunch Recipes Chronic Kidney Diseases KidsHealth > For Kids > Chronic Kidney Diseases Print ... re talking about your kidneys. What Are the Kidneys? Your kidneys are tucked under your lower ribs ...
Resources - kidney disease ... The following organizations are good resources for information on kidney disease: National Kidney Disease Education Program -- www.nkdep.nih.gov National Kidney Foundation -- www.kidney.org National ...
How Kidney Cell Death Induces Renal Necroinflammation.
Mulay, Shrikant R; Kumar, Santhosh V; Lech, Maciej; Desai, Jyaysi; Anders, Hans-Joachim
The nephrons of the kidney are independent functional units harboring cells of a low turnover during homeostasis. As such, physiological renal cell death is a rather rare event and dead cells are flushed away rapidly with the urinary flow. Renal cell necrosis occurs in acute kidney injuries such as thrombotic microangiopathies, necrotizing glomerulonephritis, or tubular necrosis. All of these are associated with intense intrarenal inflammation, which contributes to further renal cell loss, an autoamplifying process referred to as necroinflammation. But how does renal cell necrosis trigger inflammation? Here, we discuss the role of danger-associated molecular patterns (DAMPs), mitochondrial (mito)-DAMPs, and alarmins, as well as their respective pattern recognition receptors. The capacity of DAMPs and alarmins to trigger cytokine and chemokine release initiates the recruitment of leukocytes into the kidney that further amplify necroinflammation. Infiltrating neutrophils often undergo neutrophil extracellular trap formation associated with neutrophil death or necroptosis, which implies a release of histones, which act not only as DAMPs but also elicit direct cytotoxic effects on renal cells, namely endothelial cells. Proinflammatory macrophages and eventually cytotoxic T cells further drive kidney cell death and inflammation. Dissecting the molecular mechanisms of necroinflammation may help to identify the best therapeutic targets to limit nephron loss in kidney injury. PMID:27339382
A new geographic and host record for infectious pancreatic necrosis
Parisot, T.J.; Yasutake, W.T.; Bressler, V.
The occurrence of infectious pancreatic necrosis in rainbow trout (Salmo gairdneri), brook trout (Salvelinus fontinalis), and cutthroat trout (Salmo clarki) has been experimentally authenticated for the first time in the western United States. The cutthroat trout represents a new host. Brook trout fin tissue culture inoculated with bacteria-free filtrate from the diseased fish tissue showed marked degenerative changes after 24 hours. Chinook salmon (Oncorhynchus tshawytscha), kokanee (O. nerka), and silver salmon (O. kisutch) were not susceptible to the virus when inoculated. Histologically, extensive pancreatic necrosis was observed in the original and experimental materials, but striated muscle hyalinization was detected only in the original material.
... kidney or ureter. It uses sound or shock waves to break up stones. Then, the stone fragments ... the urine. It is also called extracorporeal shock-wave lithotripsy or ESWL. Procedures performed by passing a ...
... series References Barry JM, Conlin MJ. In: Renal transplantation. Wein AJ, ed. Campbell-Walsh Urology . 10th ed. ... M. Editorial team. Related MedlinePlus Health Topics Kidney Transplantation Browse the Encyclopedia A.D.A.M., Inc. ...
Herpesviral Hematopoietic Necrosis in Goldfish in Switzerland: Early Lesions in Clinically Normal Goldfish (Carassius auratus).
Giovannini, S; Bergmann, S M; Keeling, C; Lany, C; Schütze, H; Schmidt-Posthaus, H
Cyprinid herpesvirus 2 is a pathogen of goldfish, inducing a disease referred to as herpesviral hematopoietic necrosis. The disease is described so far in Japan, North America, Taiwan, Australia, the United Kingdom, and recently also Italy. Here the authors describe histologic lesions in clinically affected fish in comparison with clinically normal but virus DNA-positive goldfish in Switzerland. While necrosis or enhanced single-cell necrosis in the hematopoietic tissue in the pronephros or mesonephros was evident in dead and sick animals, in clinically normal goldfish, only single-cell necrosis was observed. Virus DNA was demonstrated in dead as well as clinically affected and subclinically infected goldfish by polymerase chain reaction and in situ hybridization. This study identifies the presence of goldfish herpesvirus in Switzerland and highlights the fact that the virus might be more widespread than assumed, as clinically normal goldfish can also carry cyprinid herpesvirus 2, showing histologically similar lesions but of lesser extent and severity. PMID:26553521
Optical Coherence Tomography in Kidney Transplantation
NASA Astrophysics Data System (ADS)
Andrews, Peter M.; Wierwille, Jeremiah; Chen, Yu
End-stage renal disease (ESRD) is associated with both high mortality rates and an enormous economic burden [1]. The preferred treatment option for ESRD that can extend patients' lives and improve their quality of life is kidney transplantation. However, organ shortages continue to pose a major problem in kidney transplantation. Most kidneys for transplantation come from heart-beating cadavers. Although non-heart-beating cadavers represent a potentially large pool of donor kidneys, these kidneys are not often used due to the unknown extent of damage to the renal tubules (i.e., acute tubular necrosis or "ATN") induced by ischemia (i.e., lack of blood flow). Also, ischemic insult suffered by kidneys awaiting transplantation frequently causes ATN that leads to varying degrees of delayed graft function (DGF) after transplantation. Finally, ATN represents a significant risk for eventual graft and patient survival [2, 3] and can be difficult to discern from rejection. In present clinical practice, there is no reliable real-time test to determine the viability of donor kidneys and whether or not donor kidneys might exhibit ATN. Therefore, there is a critical need for an objective and reliable real-time test to predict ATN to use these organs safely and utilize the donor pool optimally. In this review, we provided preliminary data indicating that OCT can be used to predict the post-transplant function of kidneys used in transplantation.
Virus-like particles associated with heart and skeletal muscle inflammation (HSMI).
Watanabe, K; Karlsen, M; Devold, M; Isdal, E; Litlabø, A; Nylund, A
The first cases of heart and skeletal muscle inflammation (HSMI), in Atlantic salmon Salmo salar were registered in 1999 in the Hitra/Frøya area of Norway. The disease has since spread south to Rogaland, i.e. the southernmost county with salmon farming in Norway. The disease outbreaks usually start 5 to 9 mo after release into seawater but may occur as early as 2 wk after sea release. The present study focuses on possible pathogens associated with HSMI. It was not possible to find any parasites or bacteria that could explain HSMI, and none of the well-known viruses (infectious salmon anaemia virus, Norwegian salmonid alphavirus, infectious pancreatic necrosis virus, Atlantic salmonid paramyxovirus) were consistently present. Use of transmission electron microscopy showed the presence of epitheliocystis agent in 3 of 4 farms included in this study, and several virus-like particles. Type I and Type II virus particles, previously described for salmon suffering from haemorrhagic smolt syndrome (HSS), and erythrocytic inclusion body syndrome (EIBS) virus were consistently present in salmon suffering from HSMI in all 4 farms included in this study. The 2 HSS viruses (Type I and Type II) were also cultured in Atlantic salmon kidney (ASK) cells from salmon suffering from HSMI. However, a causal relationship between the observed virus particles and HSMI remains to be demonstrated. PMID:16903229
On the relation of necrosis and inflammation to denaturation of proteins.
Necrosis of the skin was produced by the injection of measured quantities of electrolytes and of amino compounds into the dermis, and the relative ability of these substances to produce it was determined. Inflammation characterized by edema and accumulation of leucocytes accompanied necrosis. The ability of electrolytes to produce necrosis was found to increase with the valence of their basic ion, and in this respect was in accord with their ability to denature proteins. The quantity of different electrolytes needed to produce necrosis varied in the same order as the molar concentration of these electrolytes, that is isotonic with liver or kidney cells. Necrosis caused by amino compounds occurred with similar relation to the isotonicity of liver cells. In this as in other relations the cells acted as osmometers. The foregoing relations indicate that denaturation of proteins, necrosis of living tissue, and osmotic activity of liver or kidney cells are determined by molecular weight, valence, and ion-dissociation of electrolytes, that is, by the factors that determine the colligative properties of electrolytes. Agents such as turpentine, mustard, or croton oil and some halogen substitution compounds of methyl that are insoluble in water and soluble in lipoids have produced skin necrosis and inflammation. PMID:14482110
A Case Report of a Middle East Respiratory Syndrome Survivor with Kidney Biopsy Results
A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications. PMID:27051251
Walled-off pancreatic necrosis.
Ramia, J M; de la Plaza, R; Quiñones-Sampedro, J E; Ramiro, C; Veguillas, P; García-Parreño, J
Acute severe pancreatitits may be complicated by the development of 'walled-off pancreatic necrosis' (WOPN), which is characterised by a mixture of solid components and fluids on imaging studies as a consequence of organised pancreatic tissue necrosis. We present here an overview of the definition, clinical features, and diagnostic and therapeutic management of this clinical condition, which is mostly based on consensus as adequate clinical trials are lacking. PMID:22641624
Tumor necrosis factor-alpha genetic predisposing factors can influence clinical severity in nephropathia epidemica.
Maes, Piet; Clement, Jan; Groeneveld, Paul H P; Colson, Paul; Huizinga, Tom W J; Van Ranst, Marc
Severe human infection with Hantavirus is characterized by high fever, cold chills, thrombocytopenia, arterial hypotension, acute renal failure, and/or adult respiratory distress syndrome (ARDS)-like pulmonary involvement, but the clinical course varies greatly between individuals. We investigated whether genetically determined differences in tumor necrosis factor (TNF)-alpha production can influence the severity of Hantavirus disease. We studied a TNF-alpha single-nucleotide promoter polymorphism (SNP) at position -238 (a guanine [G]-to-adenine [A] transition) and ex vivo TNF-alpha production in a recall study of 36 Belgian patients who had a serologically proven form of Puumala virus-induced Hantavirus infection with the kidney as main target organ. In our study, the highest creatinine levels were found in patients with the lowest ex vivo TNF-alpha production. Creatinine levels correlated inversely with TNF-alpha production (R = -0.35, p < 0.05). The number of thrombocytes was significantly lower in patients with the GA-238 genotype (low TNF-alpha producers) compared with patients with the GG-238 genotype. In our study, genetically determined low production of TNF-alpha was associated with some parameters indicating a more severe clinical course of Puumala Hantavirus infection in humans, possibly by impaired activation of TNF-alpha-dependent antiviral mechanisms, which could in turn result in decreased clearance of Hantavirus. PMID:16987073
Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis
Coisy, Solène; Ebran, Jean-Marc; Milea, Dan
Introduction Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. Case Report A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment. PMID:24926266
Cysts - kidneys; Kidney - polycystic; Autosomal dominant polycystic kidney disease; ADPKD ... Polycystic kidney disease (PKD) is passed down through families (inherited). The 2 inherited forms of PKD are autosomal dominant ...
... Story" 5 Things to Know About Zika & Pregnancy Kidney Stones KidsHealth > For Parents > Kidney Stones Print A ... remove the stones from their urinary tracts. How Kidney Stones Form It's the kidneys' job to remove ...
... Nephrology American Kidney Fund National Kidney Foundation MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... Disease Organizations . (PDF, 345 KB) Alternate Language URL Kidney Stones in Children Page Content On this page: ...
Extraintestinal Complications: Kidney Disorders
... Extraintestinal Complications: Kidney Disorders Go Back Extraintestinal Complications: Kidney Disorders Email Print + Share The kidneys filter the ... but some less serious ones occur more frequently. Kidney stones These are probably the most commonly encountered ...
Chronic kidney disease is the slow loss of kidney function over time. The main job of the kidneys is to ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some time. ...
Polycystic Kidney Disease (PKD)
MENU Return to Web version Polycystic Kidney Disease Overview What is polycystic kidney disease? Polycystic kidney disease (PKD) is an inherited disease that affects the kidneys. Sacs of fluid (called ...
... Links Take the first step Alternate Language URL Kidney Disease Basics Page Content Your kidneys filter extra water ... blood pressure are the most common causes of kidney disease. These conditions can slowly damage the kidneys over ...
... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...
... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...
... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...
... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...
... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...
... a kidney transplant or blood-filtering treatments called dialysis. The two main types of PKD are autosomal ... so people with kidney failure must receive either dialysis or a kidney transplant to replace kidney function. ...
Renal Papillary Necrosis Caused by Protein C Deficiency Leading to Recurrent Hydronephrosis
Olorunnisomo, Vincent; Fowle, Evan James; Modica, Ippolito; Meisels, Ira; Gupta, Mantu
Abstract A patient with history of a solitary functioning kidney and protein C deficiency (PCD) presented with recurrent severe hydronephrosis causing acute kidney injury upon chronic kidney disease. Work-up with endoscopic evaluation revealed renal papillary necrosis (RPN) and sloughed renal papillae to be the true cause of the recurrent obstruction. Pathologic evaluation of the sloughed tissue confirmed the diagnosis of RPN. This is the first case reported in the literature illustrating the unique presentation of RPN in the setting of PCD. PMID:27579411
Renal Papillary Necrosis Caused by Protein C Deficiency Leading to Recurrent Hydronephrosis.
Chugh, Rohit Kumar; Olorunnisomo, Vincent; Fowle, Evan James; Modica, Ippolito; Meisels, Ira; Gupta, Mantu
A patient with history of a solitary functioning kidney and protein C deficiency (PCD) presented with recurrent severe hydronephrosis causing acute kidney injury upon chronic kidney disease. Work-up with endoscopic evaluation revealed renal papillary necrosis (RPN) and sloughed renal papillae to be the true cause of the recurrent obstruction. Pathologic evaluation of the sloughed tissue confirmed the diagnosis of RPN. This is the first case reported in the literature illustrating the unique presentation of RPN in the setting of PCD. PMID:27579411
A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the size of sand or ... A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the ...
A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the size of sand or gravel, ... A kidney stone is a solid piece of material that forms in a kidney. Kidney stones may be the size ...
Genomic profiling of tumor necrosis factor alpha (TNF-alpha) receptor and interleukin-1 receptor knockout mice reveals a link between TNF-alpha signaling and increased severity of 1918 pandemic influenza virus infection
Technology Transfer Automated Retrieval System (TEKTRAN)
The influenza pandemic of 1918-1919 was one of the worst global pandemics in recent history. The highly pathogenic nature of the 1918 virus is thought to be mediated in part by a dysregulation of the host response, including an exacerbated pro-inflammatory cytokine response. In the present study, we...
Winyard, Paul; Chitty, Lyn S
Dysplastic kidneys are common malformations affecting up to 1 in 1000 of the general population. They are part of the spectrum of Congenital Abnormalities of the Kidney and Urinary Tract (CAKUT) and an increasing number of children are being diagnosed on antenatal ultrasound. In the past, these patients may not have been detected until adulthood following investigation for other illness, or even as incidental findings at post mortem, unless there was severe bilateral dysplasia leading to Potter's sequence or renal failure in childhood. Excluding syndromic cases with defects in other organ systems, features linked to worse prognosis at presentation are: (1) bilateral disease; (2) decreased functional renal mass (which encompasses not just small kidneys but also large ones where cysts replace normal architecture); (3) lower urinary tract obstruction; and (4) anhydramnios or severe oligohydramnios. Dysplasia and renal function are dynamic and can evolve during pregnancy, so repeated assessment is necessary when pathology is expected. Worsening dimensions or decreasing amniotic fluid levels imply poorer prognosis, but there are no proven therapies during pregnancy, though vesicoamniotic shunting may be indicated with obstruction. Postnatal investigations aim to define the anatomy, which helps to estimate risks of infection and kidney function. Management might then involve observation, prophylactic antibiotics, surgery and/or renal support. Risks of renal malignancy and hypertension are low during childhood, but longer-term follow-up is needed, particularly to determine blood pressure and renal function in adulthood and pregnancy. Around 10% of cases have a family history of significant renal/urinary tract malformation. Monogenic causes include mutations in individual genes, such as TCF2/hepatocyte nuclear factor 1ss (HNF1beta), PAX2 and uroplakins, but there are also recent reports of children with compound heterozygote mutations in several renal/urinary tract
Widespread marrow necrosis during pregnancy
Knickerbocker, W.J.; Quenville, N.F.
Recently, a 22-year-old Caucasian female was referred to our Hospital two days post-partum. She had been feeling unwell during the last few days of her pregnancy and complained of multiple aches and pains, worst in the abdomen and lower back. Her admission platelet count was severely depressed and a bone biopsy showed extensive marrow necrosis with viable bony trabeculae. There was no evidence of vasculitis, vascular thrombosis, or malignancy. Widespread marrow necrosis in pregnancy followed by recovery, to our knowledge, has not been previously reported.
Black Anal Canal: Acute Necrosis
Martins, Catarina; Gonçalves, Cláudia; Alves, Paulo; Gil, Inês; Canhoto, Manuela; Silva, Filipe; Cotrim, Isabel; Amado, Cristina; Eliseu, Liliana; Vasconcelos, Helena
Acute ischemia of the rectum or anal canal resulting in necrosis is extremely uncommon because both the rectum and the anal canal have excellent blood supplies. We present a case with spontaneous necrosis of the anal canal without rectal involvement. Surgical debridement was accomplished, and the recovery was uneventful. The patient was elderly, with probable atherosclerotic arterial disease, and presented with hypotension. Due to the lack of other precipitating factors, the hypoperfusion hypothesis seems to be the most suitable in this case. To the best of our knowledge, no similar cases have been reported in the literature on this subject.
Khan, Saeed R; Pearle, Margaret S; Robertson, William G; Gambaro, Giovanni; Canales, Benjamin K; Doizi, Steeve; Traxer, Olivier; Tiselius, Hans-Göran
Kidney stones are mineral deposits in the renal calyces and pelvis that are found free or attached to the renal papillae. They contain crystalline and organic components and are formed when the urine becomes supersaturated with respect to a mineral. Calcium oxalate is the main constituent of most stones, many of which form on a foundation of calcium phosphate called Randall's plaques, which are present on the renal papillary surface. Stone formation is highly prevalent, with rates of up to 14.8% and increasing, and a recurrence rate of up to 50% within the first 5 years of the initial stone episode. Obesity, diabetes, hypertension and metabolic syndrome are considered risk factors for stone formation, which, in turn, can lead to hypertension, chronic kidney disease and end-stage renal disease. Management of symptomatic kidney stones has evolved from open surgical lithotomy to minimally invasive endourological treatments leading to a reduction in patient morbidity, improved stone-free rates and better quality of life. Prevention of recurrence requires behavioural and nutritional interventions, as well as pharmacological treatments that are specific for the type of stone. There is a great need for recurrence prevention that requires a better understanding of the mechanisms involved in stone formation to facilitate the development of more-effective drugs. PMID:27188687
Chromium-induced kidney disease
Wedeen, R.P. ); Qian, Lifen )
Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of {beta}{sub 2}-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome palters and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chromic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced chromic renal disease cannot be interpreted as evidence of the absence of such injury.
... Education Program > Learn About Kidney Disease > What Causes Kidney Disease? > Testing for Kidney Disease | Share External Link Disclaimer What ... from our online catalog . Alternate Language URL Español Testing for Kidney Disease Page Content Early kidney disease usually does not ...
[Acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection].
de Suremain, A; Somrani, R; Bourdat-Michel, G; Pinel, N; Morel-Baccard, C; Payen, V
Acute tubulointerstitial nephritis (TIN) is responsible for nearly 10% of acute renal failure (ARF) cases in children. It is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. An immune-competent 13-month-old boy was admitted to the intensive care unit for severe ARF with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. The kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, without any signs of necrosis. There were no virus inclusion bodies, no interstitial hemorrhage, and no glomerular or vascular damage. Other causes of TIN were excluded: there was no biological argument for an immunological, immune, or drug-induced cause. Adenovirus (ADV) and respiratory syncytial virus (RSV) were positive in respiratory multiplex polymerase chain reaction (PCR) in nasal aspirate but not in blood, urine, and renal tissue. The patient underwent dialysis for 10 days but the response to corticosteroid therapy was quickly observed within 48 h. The mechanism of TIN associated with virus infection is unknown. However, it may be immune-mediated to be able to link severe renal dysfunction and ADV and/or RSV invasion of the respiratory tract. PMID:25842199
Kidney failure - chronic; Renal failure - chronic; Chronic renal insufficiency; Chronic kidney failure; Chronic renal failure ... Chronic kidney disease (CKD) slowly gets worse over months or years. You may not notice any symptoms for some ...
You have two kidneys, each about the size of your fist. Their main job is to filter wastes and excess water out of ... help control blood pressure, and make hormones. Chronic kidney disease (CKD) means that your kidneys are damaged ...
... too high. Over time, this can damage your kidneys. Your kidneys clean your blood. If they are damaged, waste ... in your blood instead of leaving your body. Kidney damage from diabetes is called diabetic nephropathy. It ...
NASA Technical Reports Server (NTRS)
Todd, P.
The following aspects of kidney cell electrophoresis are discussed: (1) the development and testing of electrophoresis solutions; (2) optimization of freezing and thawing; (3) procedures for evaluation of separated kidney cells; and (4) electrophoretic mobility characterization of kidney cells.
NASA Technical Reports Server (NTRS)
Todd, P.
A kidney cell electrophoresis technique is described in four parts: (1) the development and testing of electrophoresis solutions; (2) optimization of freezing and thawing; (3) procedures for evaluation of separated kidney cells; and (4) electrophoretic mobility characteristics of kidney cells.
Kidney failure; Renal failure; Renal failure - acute; ARF; Kidney injury - acute ... There are many possible causes of kidney damage. They include: ... cholesterol (cholesterol emboli) Decreased blood flow due to very ...
... UTIs and kidney stones. [ Top ] Medications to Prevent Future Urinary Tract Infections and Kidney Stones Health care ... can recommend medications and dietary changes to prevent future UTIs and kidney stones. [ Top ] Clinical Trials The ...
... renal function using ureteral stenting, nephrostomy, surgery or dialysis. What is kidney (renal) failure? How is kidney ... as a urinary stent or kidney stone removal. Dialysis , including hemodialysis and peritoneal dialysis: These procedures remove ...
... or to have the blood filtered by machine (dialysis). Who Gets Kidney Disease? Not everyone with diabetes ... health care team. Kidney Failure Once kidneys fail, dialysis is necessary. The person must choose whether to ...
Acquired Cystic Kidney Disease
... a kidney transplant or blood-filtering treatments called dialysis. The cysts are more likely to develop in people who are on kidney dialysis. The chance of developing acquired cystic kidney disease ...
... Disease, and Other Dental Problems Diabetic Eye Disease Diabetes and Kidney Disease What are my kidneys and ... urine until releasing it through urination. How can diabetes affect my kidneys? Too much glucose , also called ...
Acute Kidney Injury Associated With Vancomycin When Laxity Leads to Injury and Findings on Kidney Biopsy.
Katikaneni, Madhavi; Lwin, Lin; Villanueva, Hugo; Yoo, Jinil
The issue of vancomycin-induced acute kidney injury (AKI) has resurged with the use of intravenous vancomycin as a first-line antibiotic, often for prolonged periods of time for the management of serious methicillin-resistant Staphylococcus aureus infections, and with a higher recommended trough level (15-20 μg/mL). We have observed 3 patients on intravenous vancomycin who developed very high trough levels (>40 μg/mL) and severe (stage 3) AKI. Those 3 patients underwent kidney biopsy for unresolving AKI, which revealed findings compatible with acute tubular necrosis. The first patient initially developed asymptomatic acute interstitial nephritis because of a concomitant antibiotic that caused worsening of kidney function, and the dose of vancomycin was not properly adjusted while staying at the nursing home. The second was an emaciated patient (BMI, 14) whose serum creatinine level was a deceptive marker of kidney function for the proper dosing of vancomycin, resulting in a toxic level. The third patient developed vancomycin-related AKI on an initially high therapeutic level, which then contributed to further rising in vancomycin level and subsequently causing severe AKI. One patient required hemodialysis, but all 3 patients ultimately recovered their kidney function significantly. A regular monitoring (preferably twice weekly) of serum creatinine and vancomycin trough level is advisable to minimize vancomycin-associated AKI, primarily acute tubular necrosis, for patients requiring prolonged administration of vancomycin (>2 weeks) on the currently recommended higher therapeutic trough levels (>15 μg/mL). PMID:26035034
Pure Ethiodized Oil-based Transcatheter Ablative Therapy in Normal Rabbit Kidneys and Kidneys Inoculated with VX-2 Carcinoma
Konya, Andras; Stephens, L. Clifton; Wright, Kenneth C.
Purpose: To evaluate the efficacy of ablation with selective arterial injection of pure ethiodized oil followed by arterial occlusion with 9:1 ethanol-Ethiodol mixture (EEM) and coil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma. Materials and Methods: All experiments were conducted with Animal Care and Use Committee approval. In six rabbits (group 1), one kidney was embolized with pure Ethiodol until capillary stasis, followed by injection of 9:1 EEM until arterial stasis and then coil placement into the main renal artery. In 12 other rabbits, one kidney was inoculated with VX-2 tumor. Ethiodol and EEM embolization and coil placement followed 7 days later (group 2, n = 6) or 11-14 days later (group 3, n = 6). Kidneys were evaluated (angiography, computed tomography, macro- and microscopy) 7 days after treatment. Results: Capillary stasis was achieved in groups 1, 2, and 3 with (mean {+-} standard deviation) 0.47 {+-} 0.03, 0.53 {+-} 0.02, and 0.56 {+-} 0.04 ml of pure Ethiodol, followed by 0.47 {+-} 0.05, 0.42 {+-} 0.03, and 0.38 {+-} 0.04 ml of EEM, respectively, which caused complete arterial occlusion in 17 of 18 kidneys. In group 1, all but one kidney showed at least 95% generalized coagulative necrosis. In group 2, all six kidneys exhibited 100% coagulative necrosis, with no viable tumor present. In group 3, 100% coagulative necrosis was present in all kidneys, with a small viable tumor in one. Conclusion: In the rabbit, selective arterial injection of pure Ethiodol can cause complete renal parenchyma and tumor ablation when it is followed by prompt, contiguous, and permanent occlusion of the arterial compartment.
Virus-like particles associated with mass mortalities of the pen shell Atrina pectinata in Japan.
Maeno, Yukio; Yurimoto, Tatsuya; Nasu, Hiroshi; Ito, Shiro; Aishima, Noboru; Matsuyama, Tomomasa; Kamaishi, Takashi; Oseko, Norihisa; Watanabe, Yasunori
Mass mortalities of the pen shell Atrina pectinata occurred in the fishing grounds of Ariake Bay, in southwestern Japan, during late spring and summer in 2003 and 2004. Histological examination revealed extensive necrosis in the epithelial cells of the kidney and gill, and impairment of the endothelial cells of the mantle arteria. Although cestode larvae belonging to the genus Tylocephalum were found in the mantle, adductor muscle, kidney, and digestive gland, their prevalence and the intensity of infection were low. Examinations of moribund pen shells for Haplosporidium spp. infection using PCR analysis and for Perkinsus spp. infection using Ray's fluid thioglycollate medium were negative. Unenveloped virus-like particles were detected by transmission electron microscopy in the cytoplasm of affected kidney and gill cells of moribund pen shells. They were icosahedral spherical and 50 to 55 nm in diameter. These virus-like particles found in moribund pen shells are different from those described in other marine mollusks, and may be the causative agent of the mass mortalities of pen shells. PMID:16956065
Keep Your Kidneys Clear: Kicking Kidney Stones
... PDF—450 kb) Hey, Parents: It's a Noisy Planet Keep Your Kidneys Clear Keep Your Kidneys Clear ... Pike Bethesda, Maryland 20892 Department of Health and Human Services Office of Communications and Public Liaison
Acute Esophageal Necrosis: An Update
Inayat, Faisal; Hurairah, Abu; Virk, Hafeez Ul Hassan
Acute esophageal necrosis (AEN) or "black esophagus" is a rare clinical entity with an unclear etiology. It is diagnosed at upper gastrointestinal endoscopy with the presence of strikingly black necrotic esophagus. The treatment is primarily medical, but the prognosis is generally poor due to advanced age and comorbid illnesses in patients who develop AEN. Herein, we discussed the implications of poor glycemic control in regards with AEN and undertook a literature review of this rare diagnosis. PMID:27583242
Friberg, L
The paper is a review of certain aspects of importance of cadmium and the kidney regarding the assessment of risks and understanding of mechanisms of action. The review discusses the following topics: history and etiology of cadmium-induced kidney dysfunction and related disorders; cadmium metabolism, metallothionein and kidney dysfunction; cadmium in urine as indicator of body burden, exposure and kidney dysfunction; cadmium levels in kidney and liver as indicators of kidney dysfunction; characteristics of early kidney dysfunction; the critical concentration concept; critical concentrations of cadmium in kidney cortex; and prognosis. PMID:6734547
Prevalent Class I-Restricted T-Cell Response to the Theiler's Virus Epitope Db:VP2121–130 in the Absence of Endogenous CD4 Help, Tumor Necrosis Factor Alpha, Gamma Interferon, Perforin, or Costimulation through CD28
Johnson, Aaron J.; Njenga, M. Kariuki; Hansen, Michael J.; Kuhns, Scott T.; Chen, Lieping; Rodriguez, Moses; Pease, Larry R.
C57BL/6 mice mount a cytotoxic T-lymphocyte (CTL) response against the Daniel's strain of Theiler's murine encephalomyelitis virus (TMEV) 7 days after infection and do not develop persistent infection or the demyelinating syndrome similar to multiple sclerosis seen in susceptible mice. The TMEV capsid peptide VP2121–130 sensitizes H-2Db+ target cells for killing by central-nervous-system-infiltrating lymphocytes (CNS-ILs) isolated from C57BL/6 mice infected intracranially. Db:VP2121–130 peptide tetramers were used to stain CD8+ CNS-ILs, revealing that 50 to 63% of these cells bear receptors specific for VP2121–130 presented in the context of Db. No T cells bearing this specificity were found in the cervical lymph nodes or spleens of TMEV-infected mice. H-2b mice lacking CD4, class II, gamma interferon, or CD28 expression are susceptible to persistent virus infection but surprisingly still generate high frequencies of CD8+, Db:VP2121–130-specific T cells. However, CD4-negative mice generate a lower frequency of Db:VP2121–130-specific T cells than do class II negative or normal H-2b animals. Resistant tumor necrosis factor alpha receptor I knockout mice also generate a high frequency of CD8+ CNS-ILs specific for Db:VP2121–130. Furthermore, normally susceptible FVB mice that express a Db transgene generate Db:VP2121–130-specific CD8+ CNS-ILs at a frequency similar to that of C57BL/6 mice. These results demonstrate that VP2121–130 presented in the context of Db is an immunodominant epitope in TMEV infection and that the frequency of the VP2121–130-specific CTLs appears to be independent of several key inflammatory mediators and genetic background but is regulated in part by the expression of CD4. PMID:10196262
[Talus necrosis and its treatment].
Trauth, J; Bläsius, K
Aetiopathogenesis of the necrosis of the talus has not yet been definitely clarified, and neither has that of the other aseptic necroses. We were able to study the aetiopathogenesis, course of the disease and therapy in 20 of our own patients by follow-up; two of these developed necrosis of the talus in both feet. We definitely excluded patients suffering from osteochondrosis dissecans. Even though fracture of the talus is on the whole relatively rare, it remains the most frequent cause of necrosis of the talus. We also found talonecrosis after surgical correction of clubfoot, after Sudeck's disease (Sudeck-Leriche syndrome, Sudeck's atrophy or dystrophy), suppurative arthritis of the ankle joint, subtalar luxation and haematogenic osteomyelitis. Only few patients required surgery. In most cases a special boot constructed for arthrodesis patients proved sufficient. Each patient developed arthrodesis to a different degree. Depending upon the complaints and stiffening of the ankle joint or of the talo-calcanonavicular joint, the capacity of the patients to be gainfully employed was reduced by an amount between 20 and 30 per cent. PMID:2905578
Cowan, Peter J.; Cooper, David K.C.; d'Apice, Anthony J.F.
Xenotransplantation using pigs as donors offers the possibility of eliminating the chronic shortage of donor kidneys, but there are several obstacles to be overcome before this goal can be achieved. Preclinical studies have shown that while porcine renal xenografts are broadly compatible physiologically, they provoke a complex rejection process involving preformed and elicited antibodies, heightened innate immune cell reactivity, dysregulated coagulation, and a strong T cell-mediated adaptive response. Furthermore, the susceptibility of the xenograft to pro-inflammatory and pro-coagulant stimuli is probably increased by cross-species molecular defects in regulatory pathways. To balance these disadvantages, xenotransplantation has at its disposal a unique tool to address particular rejection mechanisms and incompatibilities: genetic modification of the donor. This review focuses on the pathophysiology of porcine renal xenograft rejection, and on the significant genetic, pharmacological and technical progress that has been made to prolong xenograft survival. PMID:24088952
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Immunization with viral antigens: infectious haematopoietic necrosis.
Winton, J R
Infectious haematopoietic necrosis (IHN) is one of the most important viral diseases of salmonids, especially among juvenile fish where losses can be high. For over 20 years, researchers have tested a variety of preparations for control of IHN. Early vaccines consisted of killed virus and were effective when delivered by injection, but too costly to be practical on a large scale. Attenuated vaccines were developed by serial passage in cell culture and by monoclonal antibody selection. These offered excellent protection and were cost-effective, but residual virulence and uncertainty about their effects on other aquatic species made them poor candidates for licensing. Subunit vaccines using part of the IHNV glycoprotein gene cloned into E. coli or into an attenuated strain of A. salmonicida have been tested, appeared safe and were inexpensive. These vaccines were reported to provide some protection when delivered by immersion. Information on the location of antigenic sites on the glycoprotein led to trials using synthetic peptides, but these did not seem to be economically viable. Recently, plasmid vectors encoding the glycoprotein gene under control of a cytomegalovirus promoter were developed for genetic immunization. The constructs were highly protective when delivered by injection, but a more practical delivery system is needed. Thus, while several vaccine strategies have been tried in order to stimulate specific immunity against IHN, more research is needed to develop a commercially viable product for control of this important disease. PMID:9270850
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Strain differences in Shope fibroma virus. An immunopathologic study.
Strayer, D. S.; Skaletsky, E.; Sell, S.
The pathogenic effects of plaque-purified Boerlage and Patuxent strains of Shope fibroma virus (SFV) in neonatal rabbits are compared with results of previous reports which used nonpurified SFV. Clinically, the Boerlage strain produced large tumors; whereas the same dose of Patuxent strain SFV induced much smaller tumors locally. Neither virus caused metastatic or extensively invasive local spread in our study. Some Patuxent recipients died of respiratory infections prior to sacrifice. However, both groups of rabbits handled the tumor well; the tumor began regressing 15-20 days after inoculation. Histologically, the tumors produced by those viruses were identical. Patuxent strain recipients were otherwise normal. Boerlage strain recipients showed increased persistence of extramedullary hematopoiesis and scattered foci of parenchymal necrosis in their livers. They also showed considerable cell death in thymic lobules. In rabbits given Patuxent strain SFV, virus antigens were detected only in the tumor by immunohistologic examination. Boerlage viral antigens were found in the tumor and overlying skin. We also detected virus systemically in Boerlage recipients: it was present in fixed tissue phagocytes in the spleen and liver and also in parenchymal cells of the lungs, liver, and kidney. Boerlage strain SFV recipients also showed detectable virus in their thymus, both at the periphery of the thymic lobules and in the connective tissue separating thymic lobules from each other. Despite the disseminated nature of the infection, rabbits that received the latter strain fared as well as those receiving Patuxent strain SFV. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 p[353]-a Figure 8 Figure 9 Figure 1 p345-a Figure 6 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:6087669
Combined impact of hepatitis C virus genotype 1 and interleukin-6 and tumor necrosis factor-α polymorphisms on serum levels of pro-inflammatory cytokines in Brazilian HCV-infected patients.
Tarragô, Andréa Monteiro; da Costa, Allyson Guimarães; Pimentel, João Paulo Diniz; Gomes, Samara Tatielle Monteiro; Freitas, Felipe Bonfim; Lalwani, Pritesh; de Araújo, Ana Ruth S; Victória, Flamir da Silva; Victória, Marilú Barbieri; Vallinoto, Antônio Carlos Rosário; Sadahiro, Aya; Teixeira-Carvalho, Andréa; Martins-Filho, Olindo Assis; Malheiro, Adriana
We investigated the association between hepatitis C virus (HCV) genotypes and host cytokine gene polymorphisms and serum cytokine levels in patients with chronic hepatitis C. Serum IL-6, TNF-α, IL-2, IFN-γ, IL-4, IL-10, and IL-17A levels were measured in 67 HCV patients (68.2% genotype 1 [G1]) and 47 healthy controls. The HCV patients had higher IL-6, IL-2, IFN-γ, IL-10, and IL-17A levels than the controls. HCV G1 patients had higher IL-2 and IFN-γ levels than G2 patients. The -174IL6G>C, -308TNFαG>A, and -1082IL10A>G variants were similarly distributed in both groups. However, HCV patients with the -174IL6GC variant had higher IL-2 and IFN-γ levels than patients with the GG and CC variants. Additionally, HCV patients with the -308TNFαGG genotype had higher IL-17A levels than patients with the AG genotype, whereas patients with the -1082IL10GG variant had higher IL-6 levels than patients with the AA and AG variants. A significant proportion of HCV patients had high levels of both IL-2 and IFN-γ. The subgroup of HCV patients with the G1/IL6CG/TNFαGG association displayed the highest proportions of high producers of IL-2 and IFN-γ whereas the subgroup with the G1/TNFαGG profile showed high proportions of high producers of IL-6 and IL-17A. HCV patients with other HCV/cytokine genotype associations showed no particular cytokine profile. Our results suggest that HCV genotype G1 and IL-6 and TNF-α polymorphisms have a clinically relevant influence on serum pro-inflammatory cytokine profile (IL-2 and IFN-γ) in HCV patients. PMID:25193024
Acute Esophageal Necrosis Presenting With Henoch-Schönlein Purpura
Bernstein, Gregory R.; Malik, Zubair; Schey, Ron
A 63-year-old woman with abdominal pain and melena developed a palpable, purpuric rash and acute kidney injury. Skin and kidney biopsy confirmed Henoch-Schönlein purpura. Upper endoscopy revealed diffuse, circumferential, black-appearing mucosa of the esophagus consistent with acute esophageal necrosis (AEN), also known as black esophagus. AEN is a very rare cause of gastrointestinal hemorrhage with a high mortality risk. To our knowledge, there have been no prior reports of AEN associated with Henoch-Schonlein purpura or other vasculitis. PMID:26504868
Kleeman, Charles R.; Coburn, Jack W.; Brickman, Arnold S.; Lee, David B. N.; Narins, Robert G.; Ehrlich, Richard M.
The prevalence of kidney stones has steadily risen during this century; passage of a calculus and a positive family history increase the probability of recurrence. Findings from recent studies on the cause of renal calculi have stressed crystallization and crystal aggregation of stone minerals from supersaturated urine, rather than excessive organic matrix. Absence of normal urine inhibitors of calcium salts is also stressed. Formation of calcium oxalate stones is the major problem. Therapy with decreased calcium and oxalate intake, thiazides, phosphate salts and allopurinol in various combinations has substantially decreased the prevalence of recurrent stones. The rationale for the use of allopurinol is that uric acid salts enhance the tendency for calcium oxalate to crystallize from supersaturated urine. The hypercalciuria seen in 30 percent to 40 percent of patients with oxalate stones is usually caused by intestinal hyperabsorption of calcium. Although patients with uric acid calculi constitute only a small fraction of those in whom stones form, they represent a group in whom good medical therapy, based on sound physiologic principles, has proved extremely successful. Renal tubular syndromes lead to nephrocalcinosis and lithiasis through hypercalciuria, alkaline urine and hypocitraturia, the latter an inhibitor of calcium salt precipitation. Recent advances in surgical techniques are discussed, including the rationale for removing staghorn calculi. The ileal ureter and coagulum pyelolithotomy deserve special emphasis. ImagesFigure 2.Figure 4.Figure 5.Figure 7. PMID:7385835
Introduction The age of peak incidence for stone disease is 20 to 40 years, although stones are seen in all age groups. There is a male to female ratio of 3:2. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of interventions for stone removal in people with asymptomatic kidney stones? What are the effects of interventions for the removal of symptomatic renal stones? What are the effects of interventions to remove symptomatic ureteric stones? What are the effects of interventions for the management of acute renal colic? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2011 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 21 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review, we present information relating to the effectiveness and safety of the following interventions: antispasmodic drugs, extracorporeal shockwave lithotripsy, intravenous fluids, non-steroidal anti-inflammatory drugs (NSAIDs), opioids, oral fluids, percutaneous nephrolithotomy, and ureteroscopy. PMID:22075544
A novel role for the apoptosis inhibitor ARC in suppressing TNFα-induced regulated necrosis.
Kung, G; Dai, P; Deng, L; Kitsis, R N
TNFα signaling can promote apoptosis or a regulated form of necrosis. ARC (apoptosis repressor with CARD (caspase recruitment domain)) is an endogenous inhibitor of apoptosis that antagonizes both the extrinsic (death receptor) and intrinsic (mitochondrial/ER) apoptosis pathways. We discovered that ARC blocks not only apoptosis but also necrosis. TNFα-induced necrosis was abrogated by overexpression of wild-type ARC but not by a CARD mutant that is also defective for inhibition of apoptosis. Conversely, knockdown of ARC exacerbated TNFα-induced necrosis, an effect that was rescued by reconstitution with wild-type, but not CARD-defective, ARC. Similarly, depletion of ARC in vivo exacerbated necrosis caused by infection with vaccinia virus, which elicits severe tissue damage through this pathway, and sensitized mice to TNFα-induced systemic inflammatory response syndrome. The mechanism underlying these effects is an interaction of ARC with TNF receptor 1 that interferes with recruitment of RIP1, a critical mediator of TNFα-induced regulated necrosis. These findings extend the role of ARC from an apoptosis inhibitor to a regulator of the TNFα pathway and an inhibitor of TNFα-mediated regulated necrosis. PMID:24440909
The North American strain of viral hemorrhagic septicemia virus is highly pathogenic for laboratory-reared Pacific herring (Clupea pallasi)
Kocan, R.; Bradley, M.; Elder, N.; Meyers, T.; Batts, W.; Winton, J.
Specific-pathogen-free Pacific herring Clupea pallasi were reared in the laboratory from eggs and then challenged at 5, 9, and 13 months of age by waterborne exposure to low (101.5–2.5 plaque-forming units [PFU] per milliliter), medium (103.5–4.5 PFU/mL), or high (105.5–6.5 PFU/mL) levels of a North American isolate of viral hemorrhagic septicemia virus (VHSV). The fish were extremely susceptible to the virus, showing clinical disease, mortality approaching 100%, and only a limited increase in resistance with age. Mortality began 4–6 d after exposure and peaked at approximately day 7 in fish exposed to high levels of virus. Whereas the mean time to death showed a significant dose response (P < 0.001), the percent mortality and virus titers in dead fish were generally high in all groups regardless of initial challenge dose. External signs of disease were usually limited to 1–2-mm hemorrhagic areas on the lower jaw and isthmus and around the eye, but 2 of 130 infected fish exhibited extensive cutaneous hemorrhaging. Histopathologic examination of tissues from moribund fish sampled at 2–8 d after exposure revealed multifocal coagulative necrosis of hepatocytes, diffuse necrosis of interstitial hematopoietic tissues in the kidney, diffuse necrosis of the spleen, epidermis, and subcutis, and occasional necrosis of pancreatic acinar cells. Virus titers in tissues of experimentally infected herring were first detected 48 h after exposure and peaked 6-8 d after exposure at 107.7 PFU/g. Fish began shedding virus at 48 h after exposure with titers in the flow-through aquaria reaching 102.5 PFU/mL at 4–5 d after exposure, just before peak mortality. When the water flow was turned off for 3 h, titers in the water rose to 103.5 PFU/mL, and the amount of virus shed by infected fish (on average, greater than 106.5 PFU/h per fish) appeared sufficient to sustain a natural epizootic among schooling herring. Taken together, these data suggest that VHSV could be a
Autophagy protects C. elegans against necrosis during Pseudomonas aeruginosa infection
Zou, Cheng-Gang; Ma, Yi-Cheng; Dai, Li-Li; Zhang, Ke-Qin
Autophagy, a conserved pathway that delivers intracellular materials into lysosomes for degradation, is involved in development, aging, and a variety of diseases. Accumulating evidence demonstrates that autophagy plays a protective role against infectious diseases by diminishing intracellular pathogens, including bacteria, viruses, and parasites. However, the mechanism by which autophagy regulates innate immunity remains largely unknown. Here, we show that autophagy is involved in host defense against a pathogenic bacterium Pseudomonas aeruginosa in the metazoan Caenorhabditis elegans. P. aeruginosa infection induces autophagy via a conserved extracellular signal-regulated kinase (ERK). Intriguingly, impairment of autophagy does not influence the intestinal accumulation of P. aeruginosa, but instead induces intestinal necrosis. Inhibition of necrosis results in the survival of autophagy-deficient worms after P. aeruginosa infection. These findings reveal a previously unidentified role for autophagy in protection against necrosis triggered by pathogenic bacteria in C. elegans and implicate that such a function of autophagy may be conserved through the inflammatory response in diverse organisms. PMID:25114220
Cerebral radiation necrosis in pediatric patients.
Plimpton, S Reed; Stence, Nicholas; Hemenway, Molly; Hankinson, Todd C; Foreman, Nicholas; Liu, Arthur K
Radiation necrosis is a well-described toxicity following radiation therapy in the brain. There is little data regarding the incidence of radiation necrosis in pediatric patients. We retrospectively reviewed our experience with 101 children with solid brain tumors. Radiation necrosis was diagnosed by examination of magnetic resonance imaging. Median follow-up for all patients was 13 months (range 3-51). Radiation necrosis occurred in 5% (5/101) of cases with a median time to onset of 1.2 months. In three of these children, the child was symptomatic, requiring management with steroids and bevacizumab. Radiation necrosis did not correlate with the administration of chemotherapy, age at treatment, or planning treatment volume. Our experience with pediatric patients treated with radiotherapy for solid brain tumor suggests that children may have an increased likelihood to develop radiation necrosis compared to adults. PMID:23647507
Interleukin-12 inhibits hepatitis B virus replication in transgenic mice.
Cavanaugh, V J; Guidotti, L G; Chisari, F V
Interleukin-12 (IL-12) is a heterodimeric cytokine produced by antigen-presenting cells that has the ability to induce gamma interferon (IFN-gamma) secretion by T and natural killer cells and to generate normal Th1 responses. These properties suggest that IL-12 may play an important role in the immune response to many viruses, including hepatitis B virus (HBV). Recently, we have shown that HBV-specific cytotoxic T lymphocytes inhibit HBV replication in the livers of transgenic mice by a noncytolytic process that is mediated in part by IFN-gamma. In the current study, we demonstrated that the same antiviral response can be initiated by recombinant murine IL-12 and we showed that the antiviral effect of IL-12 extends to extrahepatic sites such as the kidney. Southern blot analyses revealed the complete disappearance of HBV replicative intermediates from liver and kidney tissues at IL-12 doses that induce little or no inflammation in these tissues. In addition, immunohistochemical analysis demonstrated the disappearance of cytoplasmic hepatitis B core antigen from both tissues after IL-12 treatment, suggesting that IL-12 either prevents the assembly or triggers the degradation of the nucleocapsid particles within which HBV replication occurs. Importantly, we demonstrated that although IFN-gamma, tumor necrosis factor alpha, and IFN-alpha/beta mRNA are induced in the liver and kidney after IL-12 administration, the antiviral effect of IL-12 is mediated principally by its ability to induce IFN-gamma production in this model. These results suggest that IL-12, through its ability to induce IFN-gamma, probably plays an important role in the antiviral immune response to HBV during natural infection. Further, since relatively nontoxic doses of recombinant IL-12 profoundly inhibit HBV replication in the liver and extrahepatic sites in this model, IL-12 may have therapeutic value as an antiviral agent for the treatment of chronic HBV infection. PMID:9060687
Adsorption to fish sperm of vertically transmitted fish viruses
Mulcahy, D.; Pascho, R.J.
More than 99 percent of a vertically transmitted fish rhabdovirus, infectious hematopoietic necrosis virus, was removed from suspension in less than 1 minute by adsorption to the surface membrane of sperm from two genera of salmonid fishes. The vertically transmitted, infectious pancreatic necrosis virus adsorbed to a lesser degree, but no adsorption occurred with a second fish rhabdovirus that is not vertically transmitted. Such adsorption may be involved in vertical transmission of these viruses.
Transformation of Madin-Darby canine kidney (MDCK) epithelial cells by Epstein-Barr virus latent membrane protein 1 (LMP1) induces expression of Ets1 and invasive growth.
Kim, K R; Yoshizaki, T; Miyamori, H; Hasegawa, K; Horikawa, T; Furukawa, M; Harada, S; Seiki, M; Sato, H
The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) has a significant role in initiating EBV-associated lymphoproliferative disease and EBV-related malignancies. In view of clinical features related to the type of EBV latency, LMP1 may influence invasiveness of EBV associated tumors categorized as types II and III as represented on nasopharyngeal carcinoma (NPC). To screen for genes associated with invasion of epithelial cells transformed by LMP1, Madin-Darby canine kidney (MDCK) epithelial cells were transformed by LMP1. Stable transfection of a LMP1 gene into MDCK cells induced morphological change from cobblestone to a long spindle-shape, reduced cell-cell adhesion and caused high cell motility. Parental MDCK cells, which form spherical cysts in three-dimensional collagen gel matrix, form branching tubules following exposure to hepatocyte growth factor (HGF). MDCK cells transformed by LMP1 showed invasive growth to form branching tubules into collagen gel without HGF-treatment. mRNA differential display and Northern hybridization identified plasminogen activator inhibitor-1 (PAI-1), urokinase type plasminogen activator (uPA) and ets1 as genes upregulated during transformation by LMP1. Expression of a dominant negative type of Etsl in LMP1-transformed cells downregulated uPA expression and cell motility. Deletion of LMP1 cytoplasmic carboxy-terminal activating region 1 (CTAR1) domain abolished transformation, but a deletion mutant lacking CTAR2 domain still retained transforming and uPA-inducing ability. Expression of Ets1 was immunolocalized in tumor cells of NPC tissue which frequently express LMP1. Taken together, it is suggested that LMP1 induces expression of Ets1 which may contribute to invasion of NPC by stimulating cell motility and uPA expression. PMID:10777210
Detection on immunoblot of new proteins from the soluble fraction of the cell recognized either by anti-liver-kidney microsome antibodies type 1 or by anti-liver cytosol antibodies type 1--relationship with hepatitis C virus infection.
Ballot, E; Desbos, A; Monier, J C
Antibodies directed against liver cytosol protein, called anti-liver cytosol type 1 (LC1 Ab), have been described by both immunofluorescence (IF) and immunodiffusion techniques in sera from patients with autoimmune hepatitis (AIH). They have never been found in association with antibodies directed against the hepatitis C virus (HCV), unlike the anti-liver-kidney microsome antibodies type 1 (LKM1 Ab), the serological marker of AIH type 2. This suggests that there are two subgroups of AIH type 2, i.e., HCV-related and non-HCV-related. In this study, immunoblotting experiments were performed using proteins from the soluble phase of the rat liver cell; 141 sera which tested positive for LKM1 Ab by IF, 24 identified as having LC1 Ab by IF, and 50 from blood donors as controls were analyzed. Three bands were stained by LC1 Ab sera more often than by the control sera, and with a statistically significant frequency. These 3 proteins were located at apparent Mr 50,000, 55,000, and 60,000. The LKM1 Ab-positive sera as defined by IF stained six bands with a statistically significant frequency compared to the controls. Their apparent Mr were 35,000, 39,000, 47,000, 50,000, 55,000, and 60,000. LKM1 Ab-positive sera which were anti-HCV negative recognized a 60,000 protein belonging to the soluble phase of the cell, with a statistically significant frequency compared to LKM1 Ab-positive sera which were anti-HCV positive. This 60,000 protein was also recognized by LC1 Ab-positive sera, which were almost always anti-HCV negative. The presence of antibodies against a 60,000 protein from the soluble phase of the cell is discussed in terms of the anti-HCV serological markers found in the sera from patients with AIH. PMID:8811044
Therapeutic targets for treating fibrotic kidney diseases
Lee, So-Young; Kim, Sung Il; Choi, Mary E.
Renal fibrosis is the hallmark of virtually all progressive kidney diseases and strongly correlates with the deterioration of kidney function. The renin-angiotensin-aldosterone system blockade is central to the current treatment of patients with chronic kidney disease (CKD) for the renoprotective effects aimed to prevent or slow progression to end-stage renal disease (ESRD). However, the incidence of CKD is still increasing, and there is a critical need for new therapeutics. Here, we review novel strategies targeting various components implicated in the fibrogenic pathway to inhibit or retard the loss of kidney function. We focus, in particular, on anti-fibrotic approaches that target transforming growth factor (TGF)-β1, a key mediator of kidney fibrosis, and exciting new data on the role of autophagy. Bone morphogenetic protein (BMP)-7 and connective tissue growth factor (CTGF) are highlighted as modulators of pro-fibrotic TGF-β activity. BMP-7 has a protective role against TGF-β1 in kidney fibrosis, whereas CTGF enhances TGF-β-mediated fibrosis. We also discuss recent advances in the development of additional strategies for anti-fibrotic therapy. These include strategies targeting chemokine pathways via CC chemokine receptor 1 and 2 to modulate the inflammatory response, inhibition of phosphodiesterase to restore nitric oxide (NO)-cyclic 3′,5′ guanosine monophosphate (cGMP) function, inhibition of NADPH oxidase 1 (Nox1) and 4 (Nox4) to suppress reactive oxygen species production, as well as inhibition of endothelin-1 or tumor necrosis factor-α to ameliorate progressive renal fibrosis. Furthermore, a brief overview of some of the biomarkers of kidney fibrosis currently being explored that may improve the ability to monitor anti-fibrotic therapies. It is hoped that evidence based on the preclinical and clinical data discussed in this review leads to novel anti-fibrotic therapies effective in patients with CKD to prevent or delay progression to ESRD. PMID
Sodium hypochlorite-induced acute kidney injury.
Peck, Brandon W; Workeneh, Biruh; Kadikoy, Huseyin; Abdellatif, Abdul
Sodium hypochlorite (bleach) is commonly used as an irrigant during dental procedures as well as a topical antiseptic agent. Although it is generally safe when applied topically, reports of accidental injection of sodium hypochlorite into tissue have been reported. Local necrosis, pain and nerve damage have been described as a result of exposure, but sodium hypo-chlorite has never been implicated as a cause of an acute kidney injury (AKI). In this report, we describe the first case of accidental sodium hypochlorite injection into the infraorbital tissue during a dental procedure that precipitated the AKI. We speculate that oxidative species induced by sodium hypochlorite caused AKI secondary to the renal tubular injury, causing mild acute tubular necrosis. PMID:24626008
Translation of satellite tobacco necrosis virus RNA modified by (not equal to)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene is inhibited in a wheat germ cell-free system
Haas, R.; Pulkrabek, P.; Takanami, Y.; Grunberger, D.
It has been shown that (not equal to)-r-7-,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) modification of rabbit globin mRNA results in inhibition of translational initiation. In order to explore the possibility that modification of the 5' cap structure was responsible for this inhibition, the naturally non-capped mRNA from satellite tobacco necrosis virus (STNV) was reacted with BPDE and translated in a wheat germ cell-free system. The extent of modification was 1.3 and 2.9 BPDE residues/molecule. High performance liquid chromatography of the modified nucleosides from enzymatically hydrolyzed STNV RNA revealed that greater than 90% of the nucleoside adducts were substituted at the exocyclic amino group of guanosine. The translational ability of the lower and higher modified STNV, measured by incorporation of (/sup 14/C)amino acids into acid-precipitable polypeptides is inhibited by 55% and 63%, respectively. Polyacrylamide gel electrophoretic analyses of the translation products indicate that predominantly full-length coat proteins are synthesized but with the carcinogen-modified STNV the amount is reduced. On the other hand, 80S initiation complex formation is not inhibited as measured by binding of the BPDE-modified STNV to ribosomes and followed by glycerol gradient centrifugation. Under these conditions, aurintricarboxylic acid completely inhibits 80S initiation complex formation in the presence of either modified or native STNV. These results suggest that inhibition of in vitro translation of BPDE-modified STNV, in contrast to that of globin mRNA, is not at the level of initiation complex formation but possibly by premature termination of growing polypeptides.
Acute oesophageal necrosis (black oesophagus).
Galtés, Ignasi; Gallego, María Ángeles; Esgueva, Raquel; Martin-Fumadó, Carles
A 54-year-old man was admitted to hospital after being found unconscious in his home. He had a history of alcoholism, multiple drug addictions, and type I diabetes mellitus. At admission, he had hyperglycaemia (550 mg/dL) with glucosuria and ketone bodies in the urine, along with septic shock refractory to bilateral alveolar infiltrates and severe respiratory failure. The patient died 24 hours post admission due to multiple organ failure, with diabetic ketoacidosis decompensated by possible respiratory infection in a patient with polytoxicomania. The autopsy confirmed the presence of acute bilateral bronchopneumonia, chronic pancreatitis, severe hepatic steatosis, and generalized congestive changes. At the oesophagus, acute oesophageal necrosis was evident. PMID:26949146
[Acute kidney injury in children].
Amira-Peco-Antić; Paripović, Dusan
Acute kidney injury (AKI) is a clinical condition considered to be the consequence of a sudden decrease (> 25%) or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN) are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary) diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis) jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP). Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients. PMID:25033598
Acute arterial occlusion - kidney
Acute renal arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... kidneys need a good blood supply. The main artery to the kidney is called the renal artery. ...
... Albumin Children and Kidney Disease Additional Kidney Information Contact Us Health Information Center Phone: 1-800-860- ... to share this content freely. March 1, 2012 Contact Us Health Information Center Phone: 1-800-860- ...
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... had a kidney stone. 2 2 Scales CD, Smith AC, Hanley JM, Saigal CS. Prevalence of kidney ... table or, less commonly, in a tub of water above the lithotripter. The lithotripter generates shock waves ...
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Diabetes and Chronic Kidney Disease
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MedlinePlus: Kidney Transplantation
... Start Here Kidney Transplant (Mayo Foundation for Medical Education and Research) Kidney Transplant (National Kidney Foundation) Treatment Methods for Kidney Failure: Transplantation (National Institute of Diabetes and Digestive and ...
Sexuality and Chronic Kidney Disease
... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...
Staying Fit with Kidney Disease
... Rate Your Risk Quiz Featured Story African Americans & Kidney Disease Did you know that African Americans are ... checks Your Kidneys and You Meetings Featured Story Kidney Walk The Kidney Walk is the nation's largest ...
A resistance gene in common bean to Clover yellow vein virus is tightly linked with bc-3 gene which confers resistance to Bean common mosaic virus
Technology Transfer Automated Retrieval System (TEKTRAN)
A strain of Clover yellow vein virus (ClYVV) that causes severe mosaic, top necrosis, stunting, and pod necrosis on infected plants has been plaguing snap bean production in the Great Lakes and Northeastern regions of the US since 2003. In preliminary virus screening experiments to identify resistan...
A rare solitary fibrous tumour of kidney.
Pathak, Tilak Bahadur; Nepal, Umesh
A solitary fibrous tumour is an unusual spindle cell neoplasm. It frequently arises from the serosal surface of pleural cavity but has recently been described in diverse extrapleural sites. Urogenital localization is rare and only 36 cases of solitary fibrous tumours of the kidney have been described on published report. We report a case of a large solitary fibrous tumour clinically and radiologically thought to be renal cell carcinoma arising in the kidney of a 30 year old female. The radical nephrectomy was performed. The tumour was a well- circumscribed, solid mass attached to the renal pelvis without necrosis and haemorrhage. Histopathologically, a spindle cell neoplasia with alternating hypo and hypercellular areas, storiform, fascicular and hemangipericytoma like growth pattern and less cellular dense collagen deposits were observed. Immunohistochemical studies revealed reactivity for CD34, CD99 and Bcl-2 protein. PMID:24362666
Acute kidney injury: A rare cause.
Mendonca, Satish; Barki, Satish; Mishra, Mayank; Kumar, R S V; Gupta, Devika; Gupta, Pooja
We present a young lady who consumed hair dye, which contained paraphenylene diamine (PPD), as a means of deliberate self-harm. This resulted in severe angio-neurotic edema for which she had to be ventilated, and thereafter developed rhabdomyolysis leading to acute kidney injury (AKI). The unusual aspect was that the patient continued to have flaccid quadriparesis and inability to regain kidney function. Renal biopsy performed 10 weeks after the dye consumption revealed severe acute tubular necrosis with myoglobin pigment casts. This suggests that PPD has a long-term effect leading to ongoing myoglobinuria, causing flaccid paralysis to persist and preventing the recovery of AKI. In such instances, timely treatment to prevent AKI in the form alkalinization of urine should be initiated promptly. Secondly, because PPD is a nondialyzable toxin, and its long-term effect necessitates its speedy removal, hemoperfusion might be helpful and is worth considering. PMID:26354573
... Acute hydronephrosis; Urinary obstruction; Unilateral hydronephrosis; Nephrolithiasis - hydronephrosis; Kidney stone - hydronephrosis; Renal calculi - hydronephrosis; Ureteral calculi - hydronephrosis; ...
Haemorrhagic smolt syndrome (HSS) in Norway: pathology and associated virus-like particles.
Nylund, A; Plarre, H; Hodneland, K; Devold, M; Aspehaug, V; Aarseth, M; Koren, C; Watanabe, K
Atlantic salmon Salmo salar pre-smolt, smolt and post-smolt, with clinical signs of haemorrhagic smolt syndrome (HSS) have been found in several locations along the Norwegian coast (Rogaland to Troms). Affected fish had pale gills and bleeding at the fin bases, but seemed to be in good physical condition with no obvious weight loss. The internal organs and body cavity showed distinct bleedings. Petechiae were found on the gastrointestinal tract, swim bladder and peritoneum, visceral adipose tissue, heart and somatic musculature. The liver was bright yellow and sometimes mottled with petechiae and ecchymoses. Acitic fluid was found in the visceral cavity and fluid was also present in the pericardial cavity. Histological examination revealed haemorrhage in most organs. The glomeruli were degenerated and the renal tubules were filled with erythrocytes. The aims of this study were to describe the pathology and discover, if possible, the aetiology of the HSS. Tissues were collected for light and transmission electron microscopy (TEM), immunofluorescence (IFAT), reverse transcription (RT)-PCR diagnostics (screening for infectious salmon anaemia virus [ISAV], viral haemorrhagic septicaemia virus [VHSV], salmon pancreas disease virus [SPDV], sleeping disease virus [SDV] and infectious haematopoetic necrosis virus [IHNV]), and tissue homogenates (heart, liver, kidney and spleen) were sterile-filtered and inoculated into cell cultures. Homogenates made from several tissues were also injected intraperitoneally into salmon and rainbow trout Oncorhynchus mykiss. The diagnostic tests revealed no consistent findings of any pathogens, with the exception of TEM which showed 2 types of virus-like particles: Type I was 50 to 60 nm in diameter and Type II about 50 nm in diameter. These virus-like particles were found in salmon from all farms affected by HSS and screened by TEM. Several different cells, blood vessel endothelial cells, endocardial cells, heart myofibres, and leukocytes
Acquired Cystic Kidney Disease
... Catherine Kelleher, M.D., University of Colorado Health Sciences Center, Denver. About the Kidney Failure Series The NIDDK Kidney Failure Series includes booklets and fact sheets that can help you learn more about treatment methods for kidney failure, complications of dialysis, financial help ...
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Mortality of captive whooping cranes caused by eastern equine encephalitis virus
Dein, F.J.; Carpenter, J.W.; Clark, G.G.; Montali, R.J.; Crabbs, C.L.; Tsai, T.F.; Docherty, D.E.
Of 39 captive whooping cranes (Grus americana), 7 died during a 7-week period (Sept 17 through Nov 4, 1984) at the Patuxent Wildlife Research Center, Laurel, Md. Before their deaths, 4 cranes did not develop clinical signs, whereas the other 3 cranes were lethargic and ataxic, with high aspartate transaminase, gamma-glutamyl transferase, and lactic acid dehydrogenase activities, and high uric acid concentrations. Necropsies indicated that the birds had ascites, intestinal mucosal discoloration, fat depletion, hepatomegaly, splenomegaly, and visceral gout. Microscopically, extensive necrosis and inflammation were seen in many visceral organs; the CNS was not affected. Eastern equine encephalitis (EEE) virus was isolated from specimens of the livers, kidneys, lungs, brains, and intestines of 4 of the 7 birds that died, and EEE virus-neutralizing antibody was detected in 14 (44%) of the 32 surviving birds. Other infectious or toxic agents were not found. Morbidity or mortality was not detected in 240 sandhill cranes (Grus canadensis) interspersed among the whooping cranes; however, 13 of the 32 sandhill cranes evaluated had EEE virus-neutralizing antibody. Of the 41 wild birds evaluated in the area, 3 (4%) had EEE virus-neutralizing antibody. Immature Culiseta melanura (the most probable mosquito vector) were found in scattered foci 5 km from the research center.
Magnetic resonance imaging of the kidneys
Leung, A.W.L.; Bydder, G.M.; Steinter, R.E.; Bryant, D.J.; Young, I.R.
A study of the magnetic resonance imaging (MRI) appearance of the kidneys in six normal volunteers and 52 patients is reported. Corticomedullary differentiation was seen with the inversion-recovery (IR 1400/400) sequence in the normal volunteers and in patients with functioning transplanted kidneys and acute tubular necrosis. Partial or total loss of corticomedullary differentiation was seen in glomerulonephritis, acute and chronic renal failure, renal artery stenosis, and transplant rejection. The T1 of the kidneys was increased in glomerulonephritis with neuphrotic syndrome, but the T1 was within the normal range for renal medulla in glomerulonephritis without nephrotic syndrome, renal artery stenosis, and chronic renal failure. A large staghorn calculus was demonstrated with MRI, but small calculi were not seen. Fluid within the hydonephrosis, simple renal cysts, and polycystic kidneys displayed very low signal intensity and long T1 values. Tumors displayed varied appearances. Hypernephromas were shown to be hypo- or hyperintense with the renal medulla on the IR 1400/400 sequence. After intravenous injection of gadolinium-DTPA, there was marked decrease in the tumor T1.
Clinical, pathological, and immunohistochemical findings in bald eagles (Haliaeetus leucocephalus) and golden eagles (Aquila chrysaetos) naturally infected with West Nile virus.
Wünschmann, Arno; Timurkaan, Necati; Armien, Aníbal G; Bueno Padilla, Irene; Glaser, Amy; Redig, Patrick T
Fifteen bald eagles (Haliaeetus leucocephalus) and 3 golden eagles (Aquila chrysaetos) were diagnosed with West Nile disease based on 1) presence of lesions in brain, eyes, and heart, 2) viral antigen detection in brain, eyes, heart, kidney, and/or liver by immunohistochemical staining, 3) detection of viral RNA in tissue samples and/or cerebrospinal fluid (CSF) by polymerase chain reaction, and/or 4) detection of West Nile virus (WNV)-specific antibodies in CSF by serum neutralization assay. West Nile virus-associated gross lesions included cerebral pan-necrosis with hydrocephalus ex vacuo (7/15 bald eagles), fibrin exudation into the fundus in 1 golden eagle, retinal scarring in 1 bald eagle, and myocardial pallor and rounded heart apex in 4 bald eagles. Histologic lesions included lymphoplasmacytic encephalitis, most prominently in the cerebrum (17 eagles), lymphoplasmacytic pectenitis and choroiditis (15 and 8 eagles, respectively), and myocarditis (12 eagles). West Nile virus antigen was detected in the majority of the eagles in neurons of the brain (cerebrum and cerebellum), and less commonly present in neurons of the retina, tubular epithelial cells of the kidney, and cardiomyocytes. West Nile disease was diagnosed in 2 bald eagles based on the presence of cerebral pan-necrosis and WNV-specific antibodies in the CSF despite lacking viral antigen and RNA. In conclusion, WNV infection causes a fatal disease in bald and golden eagles. A variety of gross and histologic lesions are highly suggestive of WN disease in most eagles. A combination of detection of viral antigen and/or RNA or virus-specific antibodies proved useful in confirming the diagnosis. PMID:25085868
Breeding Beans with Bruchid and Multiple Virus Resistance
Technology Transfer Automated Retrieval System (TEKTRAN)
Bean common mosaic virus (BCMV) and bean common mosaic necrosis virus (BCMNV) are worldwide threats to dry bean (Phaseolus vulgaris L.) production. Beans planted in the lowlands of Central America and the Caribbean also need resistance to Bean golden yellow mosaic virus (BGYMV). The common bean weev...
Measles Virus Induces Functional TRAIL Production by Human Dendritic Cells
Vidalain, Pierre-Olivier; Azocar, Olga; Lamouille, Barbara; Astier, Anne; Rabourdin-Combe, Chantal; Servet-Delprat, Christine
Measles virus infection induces a profound immunosuppression that can lead to serious secondary infections. Here we demonstrate that measles virus induces tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA and protein expression in human monocyte-derived dendritic cells. Moreover, measles virus-infected dendritic cells are shown to be cytotoxic via the TRAIL pathway. PMID:10590149
Yarmohamadi, Aliasghar; Rezayat, Ali Reza Akhavan; Memar, Bahram; Rahimi, Hamid Reza; Cand, PhD
A black kidney has 3 major differential diagnoses: hemosiderosis, lipofuscin pigment and melanotic renal cell carcinoma. Excluding lipofuscin, the other 2 are accompanied by an abnormal renal function. We report on a 25-year-old man who intended to donate a kidney to his cousin. On the operating room table when we incised the left flank region and exposed the kidney, we found a firm and black kidney so the operation was cancelled due to potential vascular injuries. Days after the incomplete procedure, we reviewed the donor's biochemistry and imaging to reassess his renal function, but the results showed quite normal renal function again. The result of Ham test was also negative. Two weeks later, we began the operation, removed the same left kidney and found that it was in the same conditions as it was before. We took the opportunity to send needle biopsies of the kidney for histopathologic analysis. The analysis showed a melanotic kidney without pathological changes in glomeruli and interstitium and vessels. A black kidney may result in hemosiderin, lipofuscin or melanin deposits in the kidney, which can confirm the diagnosis; however, special tests for underlying disease and renal function should be considered. Some causes of black kidney lead to abnormal function, but our patients's kidney returned to normal. PMID:24839502
Myofibroblasts in Fibrotic Kidneys
Nakagawa, Naoki; Duffield, Jeremy S
Fibrosis of the kidney glomerulus and interstitium are characteristic features of almost all chronic kidney diseases. Fibrosis is tightly associated with destruction of capillaries, inflammation, and epithelial injury which progresses to loss of nephrons, and replacement of kidney parenchyma with scar tissue. Understanding the origins and nature of the cells known as myofibroblasts that make scar tissue is central to development of new therapeutics for kidney disease. Whereas many cell lineages in the body have become defined by well-established markers, myofibroblasts have been much harder to identify with certainty. Recent insights from genetic fate mapping and the use of dynamic reporting of cells that make fibrillar collagen in mice have identified with greater clarity the major population of myofibroblasts and their precursors in the kidney. This review will explore the nature of these cells in health and disease of the kidney to underst and their central role in the pathogenesis of kidney disease. PMID:24187654
Prediction of pancreatic necrosis by dynamic pancreatography.
Bradley, E L; Murphy, F; Ferguson, C
Parenchymal necrosis has recently been recognized as the principal determinant of the incidence of secondary infection in acute pancreatitis. Because secondary infection of pancreatic necrosis accounts for more than 80% of all deaths from acute pancreatitis, a method for determining the presence or absence of parenchymal necrosis would offer considerable prognostic and therapeutic information. Thirty seven patients with unequivocal acute pancreatitis and five normal controls were prospectively studied with intravenous bolus, contrast-enhanced computed tomography (dynamic pancreatography). In the absence of pancreatic necrosis, there were no significant differences in parenchymal enhancement between any of the following patient groups: controls (5), uncomplicated pancreatitis (20), pancreatic abscess (7), or peripancreatic necrosis (4)(p less than 0.05). On the other hand, pancreatic parenchymal enhancement was significantly reduced or absent in all six patients with segmental or diffuse pancreatic necrosis (p less than 0.05). Postcontrast pancreatic parenchymal enhancement was also found to be inversely correlated with the number of Ranson signs (p less than 0.001). Dynamic pancreatography offers prognostic information and is a safe and reliable technique for predicting the presence or absence of pancreatic parenchymal necrosis. Images Figs. 1A and B. Figs. 3A and B. Figs. 4A and B. Fig. 5. Figs. 6A and B. Fig. 7. PMID:2802834
Choosing a Treatment for Kidney Failure
... For Kidney Failure www.kidney.org National Kidney Foundation's Kidney Disease Outcomes Quality Initiative Did you know that the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF- KDOQI)™ has ...
Failure to visualize acutely injured kidneys with technetium-99m DMSA does not preclude recoverable function
Taylor, A. Jr.; Akiya, F.; Gregory, M.C.
A 35-yr-old patient developed severe acute tubular necrosis requiring hemodialysis. A (99mTc)dimercaptosuccinic acid scan of the kidneys showed no renal uptake at 4 or 24 hr, but the patient subsequently recovered normal renal function as judged by a normal serum creatinine. Based on this case report and a review of the literature, one cannot assume irreversible loss of function in patients with acute renal failure, based on the absence of radiopharmaceutical uptake by the kidneys.
[Palatal necrosis in children. Case report].
Sancho, M A; Parri, F J; Raigosa, J M; Lerena, J; Cacéres, F; Muñoz, M E
Palate necrosis as a consequence of palate infection it's an exceptional condition about there's not too much references at literature. We present a case of a 6 months old child who present a palatal necrosis after a supurative medial otitis that involved hard and soft palate, with positive culture for Pseudomona aeruginosa causing a almost complete absence of the palate that simulate a bilateral palatal cleft. PMID:16846136
Imaging Tumor Necrosis with Ferumoxytol
Aghighi, Maryam; Golovko, Daniel; Ansari, Celina; Marina, Neyssa M.; Pisani, Laura; Kurlander, Lonnie; Klenk, Christopher; Bhaumik, Srabani; Wendland, Michael; Daldrup-Link, Heike E.
showed similar findings with high T1 signal in areas of tumor necrosis and low signal in areas of intracellularly compartmentalized iron. Conclusion Differential T1- and T2-enhancement patterns of USPIO in tumors enable conclusions about their intracellular and extracellular location. This information can be used to characterize the composition of the tumor microenvironment. PMID:26569397
Artificial transmission to and susceptibility of Puget Sound fish to viral erythrocytic necrosis (VEN)
MacMillian, John R.; Mulcahy, Dan
In Puget Sound, Wash., the incidence of viral erythrocytic necrosis (VEN) varied geographically from 0 to 17% in chum salmon (Oncorhynchus keta) and from 4 to 59% in Pacific herring (Clupea harengus pallasi). The disease was experimentally transmitted by intraperitoneal injection to chum, pink (O. gorbuscha), coho (O. kisutch), chinook (O. tshawytscha), sockeye (O. nerka), and Atlantic (Salmo salar) salmon, and rainbow (S. gairdneri), brown (S. trutta), and brook (Salvelinus fontinalis) trout. The disease was transmitted to chum salmon and brook trout by waterborne virus. Virus obtained from herring was experimentally transmitted into chum salmon by intraperitoneal injection. Key words: viral erythrocytic necrosis, fish disease, transmission
Viral erythrocytic necrosis: Chapter 2.2.7
Winton, James R.; Hershberger, Paul K.
In spite of extensive efforts, the etiological agent of VEN has not been propagated in fish cell lines making its characterization difficult. However, transmission electron microscopy (TEM) of red blood cells from diseased fish convincingly demonstrates the presence of iridovirus-like particles that have been given the name erythrocytic necrosis virus (ENV). While the ENV virions in red blood cells of various species of fish from differing geographic locations may appear morphologically distinct (Smail 1982; Wolf 1988), at least one strain of ENV has now been partially sequenced, confirming it to be a member of the family Iridoviridae (Emmenegger et al. in press). However, the genetic relatedness of ENV from various fish hosts has not yet been investigated.
Antiviral selection in the management of acute retinal necrosis
Tam, Patrick MK; Hooper, Claire Y; Lightman, Susan
There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised. PMID:20169044
Good visual outcome in an immunocompromised patient with bilateral acute retinal necrosis syndrome: A case report
Marrocos de Aragão, Ricardo E.; Barreira, Ieda M.A.; Arrais, Barbara L.A.; Pereira, Leidiane A.; Ramos, Carine S.
Acute retinal necrosis (ARN) is an uncommon necrotizing, fulminant retinopathy caused by the herpes simplex virus types 1 or 2 or by the varicella zoster vírus with visually devastating consequences. Generally it occurs in patients who are systemically healthy, but occasionally occurs in immunocompromised host. We report a case of bilateral ARN in a patient with AIDS with a good final visual outcome. PMID:25278806
Cytomegalovirus implicated in a case of progressive outer retinal necrosis (PORN).
Sfeir, Maroun
Progressive outer retinal necrosis, also known as PORN, has been described as a variant of necrotizing herpetic retinopathy, occurring particularly in patients with acquired immune deficiency syndrome (AIDS). Although the etiologic organism has been reported to be Varicella-zoster virus, cytomegalovirus (CMV) can be an etiologic agent. Our case illustrates the occurrence of two opportunistic infections: PORN associated with CMV and Mycobacterium avium intracellulare duodenitis in a patient with uncontrolled HIV infection. PMID:26209386
Diabetic nephropathy; Nephropathy - diabetic; Diabetic glomerulosclerosis; Kimmelstiel-Wilson disease ... Diabetic kidney disease is a major cause of sickness and death in people with diabetes. It can ...
Molecular determinants of acute kidney injury
Husi, Holger; Human, Christin
Abstract: Background: Acute kidney injury (AKI) is a condition that leads to a rapid deterioration of renal function associated with impairment to maintain electrolyte and acid balance, and, if left untreated, ultimately irreversible kidney damage and renal necrosis. There are a number of causes that can trigger AKI, ranging from underlying conditions as well as trauma and surgery. Specifically, the global rise in surgical procedures led to a substantial increase of AKI incidence rates, which in turn impacts on mortality rates, quality of life and economic costs to the healthcare system. However, no effective therapy for AKI exists. Current approaches, such as pharmacological intervention, help in alleviating symptoms in slowing down the progression, but do not prevent or reverse AKI-induced organ damage. Methods: An in-depth understanding of the molecular machinery involved in and modulated by AKI induction and progression is necessary to specifically pharmacologically target key molecules. A major hurdle to devise a successful strategy is the multifactorial and complex nature of the disorder itself, whereby the activation of a number of seemingly independent molecular pathways in the kidney leads to apoptotic and necrotic events. Results: The renin-angiotensin-aldosterone-system (RAAS) axis appears to be a common element, leading to downstream events such as triggers of immune responses via the NFB pathway. Other pathways intricately linked with AKI-induction and progression are the tumor necrosis factor alpha (TNF α) and transforming growth factor beta (TGF β) signaling cascades, as well as a number of other modulators. Surprisingly, it has been shown that the involvement of the glutamatergic axis, believed to be mainly a component of the neurological system, is also a major contributor. Conclusions: Here we address the current understanding of the molecular pathways evoked in AKI, their interplay, and the potential to pharmacologically intervene in the
Clinical Scenarios in Acute Kidney Injury: Parenchymal Acute Kidney Injury-Tubulo-Interstitial Diseases.
Meola, Mario; Samoni, Sara; Petrucci, Ilaria; Ronco, Claudio
Acute tubular necrosis (ATN) is the most common type of acute kidney injury (AKI) related to parenchymal damage (90% of cases). It may be due to a direct kidney injury, such as sepsis, drugs, toxins, contrast media, hemoglobinuria and myoglobinuria, or it may be the consequence of a prolonged systemic ischemic injury. Conventional ultrasound (US) shows enlarged kidneys with hypoechoic pyramids. Increased volume is largely sustained by the increase of anteroposterior diameter, while longitudinal axis usually maintains its normal length. Despite the role of color Doppler in AKI still being debated, many studies demonstrate that renal resistive indexes (RIs) vary on the basis of primary disease. Moreover, several studies assessed that higher RI values are predictive of persistent AKI. Nevertheless, due to the marked heterogeneity among the studies, further investigations focused on timing of RI measurement and test performances are needed. Acute interstitial nephritis is also a frequent cause of AKI, mainly due to non-steroidal anti-inflammatory drugs and antibiotics administration. The development of acute interstitial nephritis is due to an immunological reaction against nephritogenic exogenous antigens, processed by tubular cells. In acute interstitial nephritis, as well as in ATN, conventional US does not allow a definitive diagnosis. Kidneys appear enlarged and widely hyperechoic due to interstitial edema and inflammatory infiltration. Also, in this condition, hemodynamic changes are closely correlated to the severity and the progression of the anatomical damage. PMID:27169885
National Kidney Disease Education Program
... from our online catalog . Alternate Language URL National Kidney Disease Education Program (NKDEP) Page Content Improving the ... kidney disease. Minorities Are at Higher Risk for Kidney Disease. If you are African American, Hispanic, or ...
National Kidney Disease Education Program
... from our online catalog . Alternate Language URL National Kidney Disease Education Program (NKDEP) Page Content Improving the understanding, ... kidney disease. Minorities Are at Higher Risk for Kidney Disease. If you are African American, Hispanic, or American ...
Chronic Kidney Disease and Medicines
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Acute Kidney Injury in Patients with Cirrhosis
Russ, Kirk B.; Stevens, Todd M; Singal, Ashwani K.
Acute kidney injury (AKI) occurs commonly in patients with advanced cirrhosis and negatively impacts pre- and post-transplant outcomes. Physiologic changes that occur in patients with decompensated cirrhosis with ascites, place these patients at high risk of AKI. The most common causes of AKI in cirrhosis include prerenal injury, acute tubular necrosis (ATN), and the hepatorenal syndrome (HRS), accounting for more than 80% of AKI in this population. Distinguishing between these causes is particularly important for prognostication and treatment. Treatment of Type 1 HRS with vasoconstrictors and albumin improves short term survival and renal function in some patients while awaiting liver transplantation. Patients with HRS who fail to respond to medical therapy or those with severe renal failure of other etiology may require renal replacement therapy. Simultaneous liver kidney transplant (SLK) is needed in many of these patients to improve their post-transplant outcomes. However, the criteria to select patients who would benefit from SLK transplantation are based on consensus and lack strong evidence to support them. In this regard, novel serum and/or urinary biomarkers such as neutrophil gelatinase-associated lipocalin, interleukins-6 and 18, kidney injury molecule-1, fatty acid binding protein, and endothelin-1 are emerging with a potential for accurately differentiating common causes of AKI. Prospective studies are needed on the use of these biomarkers to predict accurately renal function recovery after liver transplantation alone in order to optimize personalized use of SLK. PMID:26623266
Lang, Joanna; Zuber, Kim; Davis, Jane
Acute kidney injury (AKI) complicates up to 20% of all hospital admissions. Responding to the increase in admissions, complications, mortality, morbidity, and cost of AKI, Kidney Disease: Improving Global Outcomes convened an expert panel to study the issue, review the literature, and publish guidelines to evaluate and treat patients with AKI in the acute setting. This article reviews those guidelines. PMID:27023656
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Amyloidosis and Kidney Disease
... Foundation Genetic and Rare Diseases Information Center MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... PDF, 345 KB) Alternate Language URL Amyloidosis and Kidney Disease Page Content On this page: What is ...
Molecular mediators of favism-induced acute kidney injury.
García-Camín, Rosa María; Goma, Montserrat; Osuna, Rosa García; Rubio-Navarro, Alfonso; Buendía, Irene; Ortiz, Alberto; Egido, Jesús; Manzarbeitia, Félix; Chevarria, Julio Leonel; Gluksmann, María Constanza; Moreno, Juan Antonio
Intolerance to fava beans in subjects with glucose-6-phosphate-dehydrogenase deficiency (favism) may lead to severe hemolytic crises and decreased renal function. Renal biopsy findings exploring the molecular mechanisms of renal damage in favism have not been previously reported. We report a case of favism-associated acute kidney injury in which renal biopsy showed acute tubular necrosis and massive iron deposits in tubular cells. Interestingly, iron deposit areas were characterized by the presence of oxidative stress markers (NADPH-p22 phox and heme-oxigenase-1) and macrophages expressing the hemoglobin scavenger receptor CD163. In addition, iron deposits, NADPH-p22 phox, hemeoxigenase- 1 and CD163 positive cells were observed in some glomeruli. These results identify both glomerular and tubular involvement in favism-associated acute kidney injury and suggest novel therapeutic targets to prevent or accelerate recovery from acute kidney injury. PMID:23006341
Hyperglycemia Increases Susceptibility to Ischemic Necrosis
Lévigne, D.; Tobalem, M.; Modarressi, A.; Pittet-Cuénod, B.
Diabetic patients are at risk for spontaneous foot ulcers, chronic wounds, infections, and tissue necrosis. Current theories suggest that the development and progression of diabetic foot ulcers are mainly caused by arteriosclerosis and peripheral neuropathy. Tissue necrosis plays a primordial role in the progression of diabetic foot ulcers but the underlying mechanisms are poorly understood. The aim of the present study was to investigate the effects of hyperglycemia per se on the susceptibility of ischemic tissue to necrosis, using a critical ischemic hind limb animal model. We inflicted the same degree of ischemia in both euglycemic and streptozotocin-induced hyperglycemic rats by resecting the external iliac, the femoral, and the saphenous arteries. Postoperative laser Doppler flowmetry of the ischemic feet showed the same degree of reduction in skin perfusion in both hyperglycemic and euglycemic animals. Nevertheless, we found a significantly higher rate of limb necrosis in hyperglycemic rats compared to euglycemic rats (71% versus 29%, resp.). In this study, we revealed that hyperglycemia per se increases the susceptibility to limb necrosis in ischemic conditions. Our results may help to better understand the physiopathology of progressive diabetic wounds and underline the importance of strict glycemic control in patients with critical limb ischemia. PMID:23509730
Targeting Cell Death Pathways for Therapeutic Intervention in Kidney Diseases.
Garg, Jay P; Vucic, Domagoj
Precise regulation of cell death and survival is essential for proper maintenance of organismal homeostasis, development, and the immune system. Deregulated cell death can lead to developmental defects, neuropathies, infections, and cancer. Kidney diseases, especially acute pathologies linked to ischemia-reperfusion injury, are among illnesses that profoundly are affected by improper regulation or execution of cell death pathways. Attempts to develop medicines for kidney diseases have been impacted by the complexity of these pathologies given the heterogeneous patient population and diverse etiologies. By analyzing cell death pathways activated in kidney diseases, we attempt to differentiate their importance for these pathologies with a goal of identifying those that have more profound impact and the best therapeutic potential. Although classic apoptosis still might be important, regulated necrosis pathways including necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-associated cell death play a significantly role in kidney diseases, especially in acute kidney pathologies. Although targeting receptor-interacting protein 1 kinase appears to be the best therapeutic strategy, combination with inhibitors of other cell death pathways is likely to bring superior benefit and possible cure to patients suffering from kidney diseases. PMID:27339381
Natural and experimental West Nile virus infection in five raptor species.
Nemeth, Nicole; Gould, Daniel; Bowen, Richard; Komar, Nicholas
We studied the effects of natural and/or experimental infections of West Nile virus (WNV) in five raptor species from July 2002 to March 2004, including American kestrels (Falco sparverius), golden eagles (Aquila chrysaetos), red-tailed hawks (Buteo jamaicensis), barn owls (Tyto alba), and great horned owls (Bubo virginianus). Birds were infected per mosquito bite, per os, or percutaneously by needle. Many experimentally infected birds developed mosquito-infectious levels of viremia (>10(5) WNV plaque forming units per ml serum) within 5 days postinoculation (DPI), and/ or shed virus per os or per cloaca. Infection of organs 15-27 days postinoculation was infrequently detected by virus isolation from spleen, kidney, skin, heart, brain, and eye in convalescent birds. Histopathologic findings varied among species and by method of infection. The most common histopathologic lesions were subacute myocarditis and encephalitis. Several birds had a more acute, severe disease condition represented by arteritis and associated with tissue degeneration and necrosis. This study demonstrates that raptor species vary in their response to WNV infection and that several modes of exposure (e.g., oral) may result in infection. Wildlife managers should recognize that, although many WNV infections are sublethal to raptors, subacute lesions could potentially reduce viability of populations. We recommend that raptor handlers consider raptors as a potential source of WNV contamination due to oral and cloacal shedding. PMID:16699143
Nonapoptotic cell death in acute kidney injury and transplantation.
Linkermann, Andreas
Acute tubular necrosis causes a loss of renal function, which clinically presents as acute kidney failure (AKI). The biochemical signaling pathways that trigger necrosis have been investigated in detail over the past 5 years. It is now clear that necrosis (regulated necrosis, RN) represents a genetically driven process that contributes to the pathophysiology of AKI. RN pathways such as necroptosis, ferroptosis, parthanatos, and mitochondrial permeability transition-induced regulated necrosis (MPT-RN) may be mechanistically distinct, and the relative contributions to overall organ damage during AKI in living organisms largely remain elusive. In a synchronized manner, some necrotic programs induce the breakdown of tubular segments and multicellular functional units, whereas others are limited to killing single cells in the tubular compartment. Importantly, the means by which a renal cell dies may have implications for the subsequent inflammatory response. In this review, the recent advances in the field of renal cell death in AKI and key enzymes that might serve as novel therapeutic targets will be discussed. As a consequence of the interference with RN, the immunogenicity of dying cells in AKI in renal transplants will be diminished, rendering inhibitors of RN indirect immunosuppressive agents. PMID:26759047
[Promoting Living Kidney Transplantation].
Lin, Chiu-Chu
Kidney transplantation is the best approach for treating patients with end stage renal disease, offering patients the best chance of returning to normal health. While the techniques used in kidney transplantation surgery are mature and highly successful, there is a severe shortage of donor organs. Statistics show a serious imbalance between organ donations and patients on the waiting list for organ transplantation. Moreover, evidence from empirical studies has shown a better transplantation outcome for patients who receive living donor transplantation than for those who receive organs from cadavers. Although using relatives as donors offers an effective way to reduce the problem of organ shortage, this strategy faces many challenges and many other factors affect the promotion of living donor transplantation. This article elaborates how cultural and psychological factors, kidney transplantation awareness, and ethics and laws impact upon living kidney donations and then proposes coping strategies for promoting living kidney transplantation. PMID:27026555
Bioengineering Kidneys for Transplantation
Madariaga, Maria Lucia L.; Ott, Harald C.
One in ten Americans suffer from chronic kidney disease, and close to 90,000 people die each year from causes related to kidney failure. Patients with end-stage renal disease are faced with two options: hemodialysis or transplantation. Unfortunately, the reach of transplantation is limited because of the shortage of donor organs and the need for immunosuppression. Bioengineered kidney grafts theoretically present a novel solution to both problems. Herein we discuss the history of bioengineering organs, the current status of bioengineered kidneys, considerations for the future of the field, and challenges to clinical translation. We hope that by integrating principles of tissue engineering, and stem cell and developmental biology, bioengineered kidney grafts will advance the field of regenerative medicine while meeting a critical clinical need. PMID:25217267
Cortical laminar necrosis following myocardial infarction.
Lattanzi, Simona; Silvestrini, Mauro; Provinciali, Leandro
The cortical laminar necrosis (CLN) is a permanent injury characterized by the selective delayed necrosis of the cerebral cortex, mainly of the third layer, and usually greater in the depths and sides of the sulci than over the crest of the gyri. The damage involves all cellular components - either neurons, glia cells and blood vessels - and results in a focal cortical band of pan-necrosis detectable in late sub-acute or chronic stages of reduced energy supply to the brain. The CLN has been described in different conditions as hypoxia, hypoglycemia and status epilepticus. At brain CT or MR scans it appears with pathognomonic highly hyperdense or T1-hyperintense lesions following the gyral anatomy of the cerebral cortex. We reported a case of CLN associated to myocardial infarct and discussed the underlying mechanisms. PMID:27375142
Regulation of necrotic cell death: p53, PARP1 and cyclophilin D-overlapping pathways of regulated necrosis?
Ying, Yuan; Padanilam, Babu J
In contrast to apoptosis and autophagy, necrotic cell death was considered to be a random, passive cell death without definable mediators. However, this dogma has been challenged by recent developments suggesting that necrotic cell death can also be a regulated process. Regulated necrosis includes multiple cell death modalities such as necroptosis, parthanatos, ferroptosis, pyroptosis, and mitochondrial permeability transition pore (MPTP)-mediated necrosis. Several distinctive executive molecules, particularly residing on the mitochondrial inner and outer membrane, amalgamating to form the MPTP have been defined. The c-subunit of the F1F0ATP synthase on the inner membrane and Bax/Bak on the outer membrane are considered to be the long sought components that form the MPTP. Opening of the MPTP results in loss of mitochondrial inner membrane potential, disruption of ATP production, increased ROS production, organelle swelling, mitochondrial dysfunction and consequent necrosis. Cyclophilin D, along with adenine nucleotide translocator and the phosphate carrier are considered to be important regulators involved in the opening of MPTP. Increased production of ROS can further trigger other necrotic pathways mediated through molecules such as PARP1, leading to irreversible cell damage. This review examines the roles of PARP1 and cyclophilin D in necrotic cell death. The hierarchical role of p53 in regulation and integration of key components of signaling pathway to elicit MPTP-mediated necrosis and ferroptosis is explored. In the context of recent insights, the indistinct role of necroptosis signaling in tubular necrosis after ischemic kidney injury is scrutinized. We conclude by discussing the participation of p53, PARP1 and cyclophilin D and their overlapping pathways to elicit MPTP-mediated necrosis and ferroptosis in acute kidney injury. PMID:27048819
[Digital necrosis in hand by uncommon mechanism].
Leroux, Maria Bibiana; Lashak, Celina; Mazzurco, Martin
A 43-year-old, non-smoking man presented with acute ischemic lesions of his left hand. He had been taking beta-blockers for his arterial hypertension. The day before the occurrence of these acute lesions, he self medicated with a drug containing ergotamine and caffeine because of a headache. About one hour after mild trauma to the hand, he noticed intense cyanosis accompanied by severe pain in the fingers that progressed to digital necrosis. Hematological tests, hand radiography, echo Doppler, and nailfold videocapillaroscopy were performed. Digital necrosis owing to an unusual combination of ischemic mechanisms is assumed. PMID:24010508
What Is Kidney Cancer (Renal Cell Carcinoma)?
... the key statistics about kidney cancer? What is kidney cancer? Kidney cancer is a cancer that starts ... and spread, see What Is Cancer? About the kidneys To understand more about kidney cancer, it helps ...
Analgesic Nephropathy (Painkillers and the Kidneys)
... American Kidney Fund National Kidney Foundation, Inc. MedlinePlus Kidney and Urologic Disease Organizations Many organizations provide support ... Alternate Language URL Analgesic Nephropathy (Painkillers and the Kidneys) Page Content On this page: Acute Kidney Failure ...
Histopathologic changes in liver and kidney tissues induced by carbaryl in Bufotes variabilis (Anura: Bufonidae).
Çakıcı, Özlem
The purpose of this work was to investigate for the first time histopathologic effects of carbaryl in liver and kidney tissues of Bufotes variabilis. After 96h following exposure to carbaryl (low dose: 0.05, medium dose: 0.1 and high dose: 0.2mg/g), the toads were euthanized and dissected. In liver tissue, vacuolization in hepatocytes, necrosis, mononuclear cell infiltration, an increase in melanomacrophage number, enlargement of sinusoids, hemorrhage and congestion were determined in exposed toads. In kidney tissue, mononuclear cell infiltration, hypertrophied Bowman's capsule cells, deformation, vacuolization, karyolysis and necrosis of renal tubule epithelium, brush border destruction, glomerular shrinkage, hemorrhage and fibrosis were observed in carbaryl-treated groups. According to this investigation, carbaryl caused histopathologic damages in liver and kidney tissues of B. variabilis. PMID:25573057
Epinephrine Injection Associated Scrotal Skin Necrosis
Gul, Murat; Kaynar, Mehmet; Sekmenli, Tamer; Ciftci, Ilhan; Goktas, Serdar
Male circumcision is among the most frequent surgical interventions throughout history. Although considered as a minor intervention, it may have complications ranging from insignificant to catastrophic. These complications can be attributed to the surgical procedure and anesthesia. In this report we present two cases of scrotal skin necrosis after lidocaine with epinephrine injection using subcutaneous ring block technique prior to circumcision. PMID:26185706
Pythium Root Rot (and Feeder Root Necrosis)
Technology Transfer Automated Retrieval System (TEKTRAN)
Pythium species cause a number of diseases on corn. Among the Pythium diseases, root rot presents the least conspicuous aboveground symptoms. Broadly defined, root rot also includes feeder root necrosis. At least 16 species of Pythium are known to cause root rot of corn. These include P. acanthicu...
Pancreatography after recovery from massive pancreatic necrosis.
Howard, J M; Wagner, S M
Massive retroperitoneal necrosis may follow life-threatening acute pancreatitis. At delayed operation, the surgeon may not be able to delineate dead pancreas from dead adipose tissue. The question arises: has "gloved hand" debridement resulted in pancreatectomy? The histologists report only "necrotic debris, of uncertain origin." To obtain objective data, pancreatography was performed in 13 patients, 10 weeks to 23 months after onset of massive pancreatic necrosis. Each patient had required delayed laparotomy for debridement and external drainage at some earlier stage of their illness. Pancreatography was correlated with the clinical assessment of diabetes and steatorrhea. Except in specific cases involving internal fistulae, pancreatography has not been previously reported in such patients. The results demonstrate that the main pancreatic duct usually maintained its normal length and configuration. Necrosis or stricture of the main duct, if it occurred, was more likely to be followed by diabetes. Steatorrhea was clinically detected in a single patient only. The necrotic tissue, up to several kilograms in wet weight, is largely dead adipose tissue. The pancreas, especially its head, is resistant to necrosis, much more resistant than is the retroperitoneal fat. PMID:2910213