APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus-1 infection
APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus-1 infection
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DOI：
10.1016/j.humimm.2010.12.008
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发表时间：
2011-03-01
期刊：
影响因子：
2.7
通讯作者：
Barbour, J. D.
中科院分区：
文献类型：
--
作者：
Gourraud, P. A.;Karaouni, A.;Barbour, J. D.
我们研究了22号染色体上APOBEC 3基因座的单核苷酸多态性（SNP），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的群体序列配对，来自96名最近HIV-1感染的未接受过治疗的成人。我们发现了存在与GA -> AA或APOBEC 3F/H特征变异相关的APOBEC 3 H连锁不平衡（LD）阻断的证据，前病毒HIV-1 vif序列中的序列变化（前10个显著SNP，显著p = 4.8 x 10（-3））。我们确定了一个常见的五位风险单倍型远端APOBEC 3 H（A3 Hrh）。这些标记物与先前描述的A3 H“RED”单倍型（含有对HIV-1 Vif具有增强的易感性的变体（E121））相比处于高LD（D' = 1; r（2）= 0.98）。单倍型分析证实了这种关联。A3 Hrh的纯合子携带者在前病毒HIV-1 vif序列上具有较低的GA->AA（A3 F/H）序列编辑（p = 0.01），并且在早期未经治疗的HIV-1感染期间随时间推移具有较低的HIV-1 RNA水平（p = 0.015混合效应模型）。这种效应可能是由于A3 H形式对HIV-1 Vif介导的序列编辑活性的病毒抑制的易感性增强，减缓了病毒多样化和逃避免疫应答。(C)2011年美国组织相容性和免疫遗传学学会。爱思唯尔公司出版All rights reserved.
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 x 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. (C) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.