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A new animal model for primary and persistent Epstein–Barr virus infection: Human EBV‐infected rabbit characteristics determined using sequential imaging and pathological analysis

Most adults have persistent Epstein–Barr virus (EBV)‐infection. Adolescents and young adults with primary EBV‐infection frequently develop infectious mononucleosis. Latent EBV‐infection is associated with various diseases, neoplasms, and hematological disorders. In vivo animal models of human EBV infection, such as non‐human primates, have had limited success. A new rabbit model for primary human EBV‐infection is described in this study. Seven male rabbits inoculated intravenously with EBV were sequentially imaged by ultrasonography and computed tomography, and examined for anti‐EBV‐VCA titer and EBV‐DNA levels in blood. Six rabbits demonstrated transient splenomegaly, increased anti‐EBV‐VCA titers and/or EBV‐DNA in blood. Transient infiltration of some EBER1‐positive lymphocytes was observed in biopsied liver tissues. After splenomegaly, two rabbits tested continuously negative, two alternatively positive and negative, and one consistently positive EBV detection in blood for 470 days. One tested negative for both EBV DNA and splenomegaly. On the 14th day, mild to moderate numbers of EBER1‐positive lymphocytes expressing LMP1, EBNA2, or ZEBRA infiltrated mainly in enlarged white pulps of two splenectomized materials. These cells included both B and T cells. EBV clonality analysis revealed an oligoclonal pattern. These indicate that EBV‐inoculated rabbits exhibiting heterogenous host reactions are a good model for primary and persistent human EBV infection. J. Med. Virol. 80:455–466, 2008. © 2008 Wiley‐Liss, Inc.