Sunday, November 28, 2010

XMRV in prostate cancer and chronic fatigue syndrome

Source: Reviews in Medical Virology
Date:   November 26, 2010

Evidence and controversies on the role of XMRV in prostate
cancer and chronic fatigue syndrome
Luis Menendez-Arias


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

(c) 2010 John Wiley&  Sons, Ltd.

No comments: