title: APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus-1 infection.
abstract: We examined single nucleotide polymorphisms (SNP) in the APOBEC3 locus on chromosome 22, paired with population sequences of pro-viral human immunodeficiency virus-1 (HIV-1) vif from peripheral blood mononuclear cells, from 96 recently HIV-1-infected treatment-naive adults. We found evidence for the existence of an APOBEC3H linkage disequilibrium (LD) block associated with variation in GA → AA, or APOBEC3F/H signature, sequence changes in pro-viral HIV-1 vif sequence (top 10 significant SNPs with a significant p = 4.8 × 10(-3)). We identified a common five position risk haplotype distal to APOBEC3H (A3Hrh). These markers were in high LD (D' = 1; r(2) = 0.98) to a previously described A3H "RED" haplotype containing a variant (E121) with enhanced susceptibility to HIV-1 Vif. This association was confirmed by a haplotype analysis. Homozygote carriers of the A3Hrh had lower GA->AA (A3F/H) sequence editing upon pro-viral HIV-1 vif sequence (p = 0.01), and lower HIV-1 RNA levels over time during early, untreated HIV-1 infection, (p = 0.015 mixed effects model). This effect may be due to enhanced susceptibility of A3H forms to HIV-1 Vif mediated viral suppression of sequence editing activity, slowing viral diversification and escape from immune responses.
authors.affiliation: Department of Neurology, San Francisco General Hospital, University of California-San Francisco, San Francisco, California, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Gourraud
authors.forename: A
authors.initials: A
authors.lastname: Karaouni
authors.forename: J M
authors.initials: JM
authors.lastname: Woo
authors.forename: T
authors.initials: T
authors.lastname: Schmidt
authors.forename: J R
authors.initials: JR
authors.lastname: Oksenberg
authors.forename: F M
authors.initials: FM
authors.lastname: Hecht
authors.forename: T J
authors.initials: TJ
authors.lastname: Liegler
authors.forename: J D
authors.initials: JD
authors.lastname: Barbour
mesh_terms: D000328:Adult; D000619:Aminohydrolases / Q000235:genetics*; D001483:Base Sequence; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D043525:Cytosine Deaminase / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D016341:Genes, vif; D014644:Genetic Variation; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011533:Proviruses / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D017422:Sequence Analysis, DNA; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D004279:DNA, Viral; D012367:RNA, Viral; D054320:vif Gene Products, Human Immunodeficiency Virus; C529313:APOBEC3H protein, human; D000619:Aminohydrolases; D043525:Cytosine Deaminase