title: Susceptibility of xenotropic murine leukemia virus-related virus (XMRV) to retroviral restriction factors.
abstract: 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.
authors.affiliation: Division of Virology, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom.
authors.forename: Harriet C T
authors.initials: HC
authors.lastname: Groom
authors.forename: Melvyn W
authors.initials: MW
authors.lastname: Yap
authors.forename: Rui Pedro
authors.initials: RP
authors.lastname: Galão
authors.forename: Stuart J D
authors.initials: SJ
authors.lastname: Neil
authors.forename: Kate N
authors.initials: KN
authors.lastname: Bishop
mesh_terms: D000071478:APOBEC Deaminases; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000998:Antiviral Agents / Q000378:metabolism*; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D002999:Clone Cells; D003564:Cytidine Deaminase / Q000378:metabolism; D043525:Cytosine Deaminase / Q000378:metabolism; D058851:GPI-Linked Proteins; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D011323:Primates; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; D053586:Virus Internalization; D014779:Virus Replication; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D000071478:APOBEC Deaminases; D015703:Antigens, CD; D000998:Antiviral Agents; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2; C477346:TRIM5 protein, human; C502889:APOBEC3 proteins, human; C503504:Apobec3 protein, mouse