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

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• 作者：Ao Zhang^a ;   ; ^b ;   ; ¹ ; Hal Bogerd^c ;   ; ¹ ; Francois Villinger^d ; Jaydip Das Gupta^b ; Beihua Dong^b ; Eric A. Klein^e ; John Hackett Jr.^f ; Gerald Schochetman^f ; Bryan R. Cullen^c ; Robert H. Silverman^a ;   ; ^b ;   ; ^{silverr@ccf.org}
• 关键词：XMRV ; APOBEC3 ; Hypermutation ; Retrovirus ; Host restriction ; Innate immunity
• 刊名：Virology
• 出版年：2011
• 出版时间：5 December 2011
• 年：2011
• 卷：421
• 期：1
• 页码：28-33
• 全文大小：934 K

文摘

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.