Evidence and controversies on the role of XMRV in prostate cancer and chronic fatigue syndrome.

The recent discovery of xenotropic murine leukaemia virus-related virus (XMRV) in prostate cancer tissues and in the blood of individuals suffering from chronic fatigue syndrome has attracted considerable interest. However, the relevance and significance of XMRV to human disease remain unclear, since the association has not been confirmed in other studies. XMRV is the first gammaretrovirus to be found in humans. XMRV and murine leukaemia viruses share similar structures and genomic organisation. Human restriction factors such as APOBEC3 or tetherin inhibit XMRV replication. Although XMRV induces low rates of transformation in cell culture, it might be able to induce cancer by low-frequency insertional activation of oncogenes or through the generation of highly active transforming viruses. A preference for regulatory regions of transcriptional active genes has been observed after a genomic-wide analysis of XMRV integration sites. Genes related to carcinogenesis and androgen signalling have been identified in the vicinity of integration sites. The XMRV genome contains a glucocorticoid responsive element, and androgens could modulate viral replication in the prostate. Evidence supporting the involvement of XMRV in chronic fatigue syndrome is still very weak, and needs further confirmation and validation. Currently approved anti-retroviral drugs such as zidovudine, tenofovir and raltegravir are efficient inhibitors of XMRV replication in vitro. These drugs might be useful to treat XMRV infection in humans. The identification of XMRV has potentially serious health implications for the implementation of novel techniques including gene therapy or xenotransplantation, while raising concerns on the need for screening donated blood to prevent transmission through transfusion.