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

Pace, C., Keller, J., Nolan, D., James, I., Gaudieri, S., Moore, C. and Mallal, S. (2006) Population level analysis of human immunodeficiency virus type 1 hypermutation and its relationship with APOBEC3G and vif genetic variation. Journal of Virology, 80 (18). pp. 9259-9269.

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    Link to Published Version: http://dx.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.

    Publication Type: Journal Article
    Murdoch Affiliation: Centre for Clinical Immunology and Biomedical Statistics
    Publisher: American Society for Microbiology
    Copyright: 2006 American Society for Microbiology
    URI: http://researchrepository.murdoch.edu.au/id/eprint/11908
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