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

dc.contributor.authorKijak, Gustavo H.
dc.contributor.authorJanini, Luiz Mário Ramos [UNIFESP]
dc.contributor.authorTovanabutra, Sodsai
dc.contributor.authorSanders-Buell, Eric
dc.contributor.authorArroyo, Miguel Angel
dc.contributor.authorRobb, Merlin L.
dc.contributor.authorMichael, Nelson L.
dc.contributor.authorBirx, Debora L.
dc.contributor.authorMcCutchan, Francine E.
dc.contributor.institutionHenry M Jackson Fdn Advancement Mil Med
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionWalter Reed Army Inst Res
dc.date.accessioned2016-01-24T13:51:29Z
dc.date.available2016-01-24T13:51:29Z
dc.date.issued2008-06-20
dc.description.abstractAPOBEC-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.en
dc.description.affiliationHenry M Jackson Fdn Advancement Mil Med, US Mil HIV Res Program, Rockville, MD 20850 USA
dc.description.affiliationUniversidade Federal de São Paulo, Paulista Sch Med, Div Infect Dis, BR-04039 São Paulo, Brazil
dc.description.affiliationWalter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Paulista Sch Med, Div Infect Dis, BR-04039 São Paulo, Brazil
dc.description.sourceWeb of Science
dc.format.extent101-111
dc.identifierhttp://dx.doi.org/10.1016/j.virol.2008.03.017
dc.identifier.citationVirology. San Diego: Academic Press Inc Elsevier Science, v. 376, n. 1, p. 101-111, 2008.
dc.identifier.doi10.1016/j.virol.2008.03.017
dc.identifier.fileWOS000256485100011.pdf
dc.identifier.issn0042-6822
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/30736
dc.identifier.wosWOS:000256485100011
dc.language.isoeng
dc.publisherElsevier B.V.
dc.relation.ispartofVirology
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.subjectHIV-1en
dc.subjecthypermutationen
dc.subjectinnate immunityen
dc.subjecthost restrictionen
dc.subjectAPOBEC3Gen
dc.subjectAPOBEC3Fen
dc.titleVariable contexts and levels of hypermutation in HIV-1 proviral genomes recovered from primary peripheral blood mononuclear cellsen
dc.typeinfo:eu-repo/semantics/article
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