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

Proc Natl Acad Sci U S A. 2010 Mar 16;107(11):5166-71. doi: 10.1073/pnas.0913650107. Epub 2010 Mar 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • APOBEC Deaminases
  • Animals
  • Antigens, CD / metabolism
  • Antiviral Agents / metabolism*
  • Antiviral Restriction Factors
  • Carrier Proteins / metabolism
  • Cell Line
  • Clone Cells
  • Cytidine Deaminase / metabolism
  • Cytosine Deaminase / metabolism
  • GPI-Linked Proteins
  • Humans
  • Leukemia Virus, Murine / physiology*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Primates
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases
  • Virus Internalization
  • Virus Replication

Substances

  • Antigens, CD
  • Antiviral Agents
  • Antiviral Restriction Factors
  • BST2 protein, human
  • Carrier Proteins
  • GPI-Linked Proteins
  • Membrane Glycoproteins
  • Tripartite Motif Proteins
  • TRIM5 protein, human
  • Ubiquitin-Protein Ligases
  • Cytosine Deaminase
  • APOBEC Deaminases
  • APOBEC3 protein, human
  • Apobec3 protein, mouse
  • Cytidine Deaminase