Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retro

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_Proc Natl Acad Sci U S A._

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2010 Mar 1. [Epub ahead of print]

Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to

retroviral restriction factors.

_Groom HC_

(http://www.ncbi.nlm.nih.gov/pubmed?term= " Groom%20HC " [Author] & itool=EntrezSystem\

2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract) ,

_Yap MW_

(http://www.ncbi.nlm.nih.gov/pubmed?term= " Yap%20MW " [Author] & itool=EntrezSystem2.\

PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract) , _Galão

RP_

(http://www.ncbi.nlm.nih.gov/pubmed?term= " Galão%20RP " [Author] & itool=EntrezSystem\

2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract) , _Neil

SJ_

(http://www.ncbi.nlm.nih.gov/pubmed?term= " Neil%20SJ " [Author] & itool=EntrezSystem2\

..PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract) , _Bishop KN_

(http://www.ncbi.nlm.nih.gov/pubmed?term= " Bishop%20KN " [Author

] & itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVAbstract) .

Division of Virology, MRC National Institute for Medical Research, London

NW7 1AA, United Kingdom.

Xenotropic murine leukemia virus-related virus (XMRV) is a recently

discovered gammaretrovirus 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 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.

We therefore investigated the susceptibility of XMRV to a panel of

different restriction factors. We found that both human APOBEC3 and tetherin

proteins are able to block XMRV replication. Expression of human TRIM5alpha,

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. 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.

PMID: 20194752 [PubMed - as supplied by publisher]