Variable contexts and levels of hypermutation in HIV-1 proviral genomes recovered from primary peripheral blood mononuclear cells
| Autor: | Eric Sanders-Buell, Miguel A. Arroyo, Luiz Mário Ramos Janini, Francine E. McCutchan, Gustavo H. Kijak, Merlin L. Robb, Nelson L. Michael, Sodsai Tovanabutra, Debora L. Birx |
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| Přispěvatelé: | Henry M Jackson Fdn Advancement Mil Med, Universidade Federal de São Paulo (UNIFESP), Walter Reed Army Inst Res |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Sequence analysis
Viral protein Molecular Sequence Data Somatic hypermutation HIV Infections Genome Viral Biology medicine.disease_cause Genome Cytidine deamination Proviruses Virology medicine Humans APOBEC3G innate immunity Genetics Mutation hypermutation Sequence Analysis DNA Reverse transcriptase Blood Leukocytes Mononuclear HIV-1 host restriction APOBEC3F |
| Zdroj: | Repositório Institucional da UNIFESP Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
| Popis: | 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. Henry M Jackson Fdn Advancement Mil Med, US Mil HIV Res Program, Rockville, MD 20850 USA Universidade Federal de São Paulo, Paulista Sch Med, Div Infect Dis, BR-04039 São Paulo, Brazil Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD 20850 USA Universidade Federal de São Paulo, Paulista Sch Med, Div Infect Dis, BR-04039 São Paulo, Brazil Web of Science |
| Databáze: | OpenAIRE |
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