Increased proportion of KIR3DS1 homozygotes in HIV-exposed uninfected individuals

Increased proportion of KIR3DS1 homozygotes in HIV-exposed uninfected individuals
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DOI:
10.1097/qad.0b013e3282f56b23
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发表时间:
2008-03-12
期刊:
影响因子:
3.8
通讯作者:
Bernard, Nicole F.
Bernard, Nicole F.
中科院分区:
医学2区
文献类型:
--
作者:
Boulet, Salix;Sharafi, Saeid;Bernard, Nicole F.

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目的:自然杀伤(NK)细胞活性在反复暴露于HIV的未感染个体中增加。鉴于主要组织相容性复合体(MHC) I类和杀伤免疫球蛋白样受体(KIR) KIR3D基因型的组合与HIV疾病进展率有关,我们评估了这些基因型是否在预防感染方面发挥作用。设计:该研究在MHC类IB和KIR3DS/L1位点对80名HIV暴露的未感染者(EU)和304名HIV原发性感染(PI)受试者进行基因分型。方法:采用序列特异性引物聚合酶链反应进行KIR3D基因分型,每个位点使用两对特异性引物。通过序列特异性寡核苷酸聚合酶链反应和测序,对Bw4和Bw6等位基因和80位氨基酸进行分型。结果:欧盟人群与PI人群KIR3D、HLA Bw4和HLA Bw4-180基因型的遗传分布比较显示,欧盟人群KIR3DS1纯合子比例(11/80,13.8%)高于PI人群(116/304,5.3%)。MHC I类和KIR3D的联合表达分析显示两个人群之间没有差异。结论:激活NK受体KIR3DS1的纯合性可能有助于在EU中观察到更活跃的NK细胞功能及其对HIV的相对抗性(C) 2008 Wolters Kluwer Health Lippincott Williams & Wilkins
Objectives: Natural killer (NK) cell activity is increased in individuals who remain uninfected despite repeated exposures to HIV. Given that a combined major histocompatibility complex (MHC) class I and killer immunoglobulin-like receptor (KIR) KIR3D genotype has been linked to rate of HIV disease progression, we assessed whether these genotypes played a role in protection from infection.Design: The study genotyped 80 HIV-exposed uninfected (EU) and 304 subjects in HIV primary infection (PI) at the MHC class IB and KIR3DS/L1 loci.Methods: KIR3D genotyping was performed by sequence-specific primer polymerase chain reaction using two pairs of specific primers for each locus. The MHC class IB locus was typed by sequence-specific oligonucleotide polymerase chain reaction and sequencing to resolve Bw4 and Bw6 alleles and the amino acid present at position 80.Results: Comparison of the genetic distribution of KIR3D, HLA Bw4 and HLA Bw4-180 genotypes in EU versus PI subjects reveal an increased proportion of KIR3DS1 homozygotes in EU (11/80, 13.8%) compared to subjects in PI (116/304, 5.3%). Analyses of combined MHC class I and KIR3D expression show no differences between the two populations.Conclusions: Homozygosity for the activating NK receptor KIR3DS1, may contribute to the more active NK cell function observed in EU and their relative resistance to HIV (C) 2008 Wolters Kluwer Health Lippincott Williams & Wilkins