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Endogenous retroviruses and human disease

Human endogenous retroviruses (HERVs) constitute up to 8% of the human genome. In general they are highly defective, but complete proviruses have also been described. Over time some transposable elements became inactive, while others retain mobility within the genome. Variably inserting in cellular genes, and differentially within the various allotypes of polymorphic genes, they may have determined inheritable, stable gene modifications. Approximately 40,000 HERV elements have been identified to date, including truncated and solitary long terminal repeats. The latter have powerful transcriptional regulatory properties, therefore they may behave as promoters and enhancers of cellular genes and interact with oncogenes. In some cases, the host has utilized the presence of these ancestrally transmitted foreign genomes to serve physiological functions, and several possible beneficial effects have been reported. On the other hand, links of some human diseases with HERVs are increasingly observed, and this review presents data on possible HERV association to human disease. Reports have shown expression of one or more HERVs in physiological or pathological conditions, in one or more body sites. A key problem is differentiating this expression as cause or effect of a particular disease. Human diseases have been related to HERVs, particularly those characterized by multifactorial etiology or dysregulated immune functions, such as multiple sclerosis, Type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, schizophrenia, cancer and hematological disorders. Convincing evidence has been found that the HERV-W family has a physiological role in early pregnancy and a role in multiple sclerosis as a cofactor and predictor of disease progression. Data available for HERVs and other diseases are attractive, but further studies are required.