MRC National Institute for Medical Research, London
Science for Health
Human restriction factors inhibit XMRV
02 March 2010
Xenotropic murine leukemia virus-Related Virus (XMRV) is a recently discovered gamma-retrovirus that has been linked to prostate cancer and chronic fatigue syndrome. This virus is therefore an important potential human pathogen and, as such, it is essential to understand its host cell tropism. Intriguingly, infectious virus has reportedly been recovered from patient-derived peripheral blood mononuclear cells. These cells express several antiviral restriction factors that are capable of inhibiting the replication of a wide range of retroviruses, including other gamma retroviruses. This raises the possibility that, similar to HIV, XMRV may have acquired resistance to restriction.
Kate Bishop (pictured) and her group, in NIMR's Division of Virology, has investigated the susceptibility of XMRV to a panel of different restriction factors. They found that both human APOBEC3 and tetherin proteins are able to block XMRV replication. Expression of human TRIM5α, however, had no effect on viral infectivity. There was no evidence that XMRV expressed countermeasures to overcome restriction. In addition, the virus was inhibited by factors from nonhuman species, including mouse Apobec3, tetherin, and Fv1 proteins. This finding presents new questions as to which cells the virus replicates in vivo, and how it evades restriction by these factors in peripheral blood mononuclear cells, particularly in the absence of obvious viral countermeasures. These results have important implications for predicting the natural target cells for XMRV replication, for relating infection to viral pathogenicity and pathology, and for the design of model systems with which to study XMRV-related diseases.
Whether a virus can infect particular cells within a specific host and the severity of the disease this may cause is dependent upon the many interactions that occur between viral and cellular factors. Restriction factors are thought to influence host susceptibility to infection, zoonotic transmission, and pathogenicity of retroviruses, and may represent previously unexplored targets for antiviral therapy. Thus, the effect of such factors on the replication of XMRV, recently identified as linked to two important human diseases—prostate cancer and CFS —is potentially significant.
Kate Bishop
Original article
The research findings are published in full in:
Harriet C. T. Groom, Melvyn W. Yap, Rui Pedro Galão, Stuart J. D. Neil, and Kate N. Bishop (2010)
Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors.
Proceedings of the National Academy of Sciences, USA epub ahead of print. Publisher abstract
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