Department of Neurology, San Francisco General Hospital, University of California-San Francisco, San Francisco, California, USA.
Hum Immunol. 2011 Mar;72(3):207-12. doi: 10.1016/j.humimm.2010.12.008. Epub 2010 Dec 15.
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.
我们研究了染色体 22 上 APOBEC3 基因座的单核苷酸多态性（SNP），并与来自外周血单核细胞的前病毒人类免疫缺陷病毒-1（HIV-1）vif 的人群序列进行配对，这些样本来自 96 名最近感染 HIV-1 的未经治疗的成年人。我们发现存在与 GA→AA 或 APOBEC3F/H 特征相关的 APOBEC3H 连锁不平衡（LD）块的证据，前病毒 HIV-1 vif 序列中的序列发生变化（前 10 个具有显著意义的 SNP，p = 4.8×10(-3)）。我们确定了 APOBEC3H 远端常见的五个位置风险单倍型（A3Hrh）。这些标记与先前描述的 A3H“RED”单倍型高度 LD（D'=1；r(2)=0.98），该单倍型包含一种变体（E121），使 HIV-1 Vif 易感性增强。这种关联通过单倍型分析得到了证实。A3Hrh 纯合子携带者在前病毒 HIV-1 vif 序列中 GA->AA（A3F/H）序列编辑减少（p=0.01），并且在未经治疗的 HIV-1 感染早期，HIV-1 RNA 水平随时间降低（p=0.015 混合效应模型）。这种效应可能是由于 A3H 形式对 HIV-1 Vif 介导的病毒抑制序列编辑活性的敏感性增强，从而减缓病毒多样化并逃避免疫反应。
