In vivo hypermutation of xenotropic murine leukemia virus-related virus DNA in peripheral blood mononuclear cells of rhesus macaque by APOBEC3 proteins.

Abstract

The gammaretrovirus, xenotropic murine leukemia virus-related virus (XMRV), replicates to high titers in some human cell lines and is able to infect non-human primates. To determine whether APOBEC3 (A3) proteins restrict XMRV infections in a non-human primate model, we sequenced proviral DNA from peripheral blood mononuclear cells of XMRV-infected rhesus macaques. Hypermutation characteristic of A3DE, A3F and A3G activities was observed in the XMRV proviral sequences in vivo. Furthermore, expression of rhesus A3DE, A3F, or A3G in human cells inhibited XMRV infection and caused hypermutation of XMRV DNA. These studies show that some rhesus A3 isoforms are highly effective against XMRV in the blood of a non-human primate model of infection and in cultured human cells.

• Authors: Ao Zhang, Hal Bogerd, Francois Villinger, Jaydip Das Gupta, Beihua Dong, Eric A Klein, John Hackett Jr, Gerald Schochetman, Bryan R Cullen, Robert H Silverman
• Journal: Virology (Virology) Vol. 421 Issue 1 Pg. 28-33 (Dec 05 2011) ISSN: 1096-0341 [Electronic] United States
• PMID: 21982221 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• DNA, Viral
• Cytosine Deaminase

Topics

• Animals
• Base Sequence
• Cell Line
• Cytosine Deaminase (genetics, metabolism)
• DNA, Viral (genetics, metabolism)
• Disease Models, Animal
• Female
• Humans
• Leukocytes, Mononuclear (enzymology, virology)
• Macaca mulatta
• Male
• Molecular Sequence Data
• Mutation
• Retroviridae Infections (enzymology, virology)
• Virus Replication
• Xenotropic murine leukemia virus-related virus (genetics, physiology)