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 DN...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2011-12, Vol.421 (1), p.28-33
Main Authors: Zhang, Ao, Bogerd, Hal, Villinger, Francois, Gupta, Jaydip Das, Dong, Beihua, Klein, Eric A, Hackett, John, Schochetman, Gerald, Cullen, Bryan R, Silverman, Robert H
Format: Article
Language:English
Subjects:
Animals
APOBEC3
Base Sequence
Cell Line
Cytosine Deaminase - genetics
Cytosine Deaminase - metabolism
Disease Models, Animal
DNA, Viral - genetics
DNA, Viral - metabolism
Female
Host restriction
Humans
Hypermutation
Infectious Disease
Innate immunity
Leukocytes, Mononuclear - enzymology
Leukocytes, Mononuclear - virology
Macaca mulatta
Male
Molecular Sequence Data
Mutation
Primates
Retroviridae Infections - enzymology
Retroviridae Infections - virology
Retrovirus
Virus Replication
Xenotropic murine leukemia virus-related virus - genetics
Xenotropic murine leukemia virus-related virus - physiology
XMRV
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2011.08.030