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

Abstract APOBEC-mediated cytidine deamination 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 re...

Full description

Saved in:
Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2008-06, Vol.376 (1), p.101-111
Main Authors: Kijak, Gustavo H, Janini, Luiz Mario, Tovanabutra, Sodsai, Sanders-Buell, Eric, Arroyo, Miguel Angel, Robb, Merlin L, Michael, Nelson L, Birx, Debora L, McCutchan, Francine E
Format: Article
Language:English
Subjects:
APOBEC3F
APOBEC3G
Blood - virology
Genome, Viral
HIV Infections - virology
HIV-1
HIV-1 - genetics
Host restriction
Human immunodeficiency virus 1
Humans
Hypermutation
Infectious Disease
Innate immunity
Leukocytes, Mononuclear - virology
Molecular Sequence Data
Mutation
Proviruses - genetics
Sequence Analysis, DNA
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract APOBEC-mediated cytidine deamination 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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2008.03.017