Population level analysis of human immunodeficiency virus type 1 hypermutation and its relationship with APOBEC3G and vif genetic variation

C. Pace; J. Keller; D. Nolan; I. James; S. Gaudieri; C. Moore; S. Mallal

doi:10.1128/JVI.00888-06

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Population level analysis of human immunodeficiency virus type 1 hypermutation and its relationship with APOBEC3G and vif genetic variation

Journal article

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Population level analysis of human immunodeficiency virus type 1 hypermutation and its relationship with APOBEC3G and vif genetic variation

C. Pace, J. Keller, D. Nolan, I. James, S. Gaudieri, C. Moore and S. Mallal

Journal of Virology, Vol.80(18), pp.9259-9269

2006

DOI: https://doi.org/10.1128/JVI.00888-06

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Abstract

APOBEC3G and APOBEC3F restrict human immunodeficiency virus type 1 (HIV-1) replication in vitro through the induction of G!92A hypermutation; however, the relevance of this host antiviral strategy to clinical HIV-1 is currently not known. Here, we describe a population level analysis of HIV-1 hypermutation in near-full-length clade B proviral DNA sequences (n = 127). G!92A hypermutation conforming to expected APOBEC3G polynucleotide sequence preferences was inferred in 9.4% (n = 12) of the HIV-1 sequences, with a further 2.4% (n = 3) conforming to APOBEC3F, and was independently associated with reduced pretreatment viremia (reduction of 0.7 log10 copies/ml; P = 0.001). Defective vif was strongly associated with HIV-1 hypermutation, with additional evidence for a contribution of vif amino acid polymorphism at residues important for APOBEC3G-vif interactions. A concurrent analysis of APOBEC3G polymorphism revealed this gene to be highly conserved at the amino acid level, although an intronic allele (6,892 C) was marginally associated with HIV-1 hypermutation. These data indicate that APOBEC3G-induced HIV-1 hypermutation represents a potent host antiviral factor in vivo and that the APOBEC3G-vif interaction may represent a valuable therapeutic target.

Details

Title: Population level analysis of human immunodeficiency virus type 1 hypermutation and its relationship with APOBEC3G and vif genetic variation
Authors/Creators: C. Pace (Author/Creator)
J. Keller (Author/Creator)
D. Nolan (Author/Creator)
I. James (Author/Creator)
S. Gaudieri (Author/Creator)
C. Moore (Author/Creator)
S. Mallal (Author/Creator)
Publication Details: Journal of Virology, Vol.80(18), pp.9259-9269
Publisher: American Society for Microbiology
Identifiers: 991005545165507891
Copyright: 2006 American Society for Microbiology
Murdoch Affiliation: Centre for Clinical Immunology and Biomedical Statistics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.1243 Integrase
Web Of Science research areas: Virology
ESI research areas: Microbiology