Variable contexts and levels of hypermutation in HIV-1 proviral genomes recovered from primary peripheral blood mononuclear cells

Variable contexts and levels of hypermutation in HIV-1 proviral genomes recovered from primary peripheral blood mononuclear cells

Autor Kijak, Gustavo H. Google Scholar
Janini, Luiz Mário Ramos Autor UNIFESP Google Scholar
Tovanabutra, Sodsai Google Scholar
Sanders-Buell, Eric Google Scholar
Arroyo, Miguel Angel Google Scholar
Robb, Merlin L. Google Scholar
Michael, Nelson L. Google Scholar
Birx, Debora L. Google Scholar
McCutchan, Francine E. Google Scholar
Instituição Henry M Jackson Fdn Advancement Mil Med
Universidade Federal de São Paulo (UNIFESP)
Walter Reed Army Inst Res
Resumo APOBEC-mediated cytidine cleamination of HIV-1 genomes during reverse transcription has been shown to be a potent mechanism of host restriction for HIV-1 infection ex vivo and in vitro. However, this defense system can be overcome by the viral protein Vif. Unlike other mechanisms of host restriction, the APOCEC-Vif interaction leaves an imprint on integrated proviruses in the form of G-A hypermutation. in the current work we systematically studied levels, contexts, and patterns of HIV-1 hypermutation in vivo. the analysis of 24 full-genome HIV-1 sequences retrieved from primary PBMCs, representing infections with several HIV-1 clades, and the inclusion of 7 cognate pairs of hypermutated/non-hypermutated sequences derived from the same patient sample, provided a comprehensive view of the characteristics of APOBEC-mediated restriction in vivo. Levels of hypermutation varied nearly 5-fold among the studied proviruses. GpG motifs were most frequently affected (22/24 proviruses). Levels of hypermutation varied across the genome. the reported twin peak pattern of hypermutation was observed in 18/24 hypermutants, but the remainder exhibited singular non-conforming patterns. These data suggest considerable complexity in the interplay of host restriction and viral defense during HIV-1 infection. (c) 2008 Elsevier Inc. All rights reserved.
Assunto HIV-1
hypermutation
innate immunity
host restriction
APOBEC3G
APOBEC3F
Idioma Inglês
Data 2008-06-20
Publicado em Virology. San Diego: Academic Press Inc Elsevier Science, v. 376, n. 1, p. 101-111, 2008.
ISSN 0042-6822 (Sherpa/Romeo, fator de impacto)
Editor Elsevier B.V.
Extensão 101-111
Fonte http://dx.doi.org/10.1016/j.virol.2008.03.017
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000256485100011
URI http://repositorio.unifesp.br/handle/11600/30736

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