Impact of a Functional KIR2DS4 Allele on Heterosexual HIV-1 Transmission among Discordant Zambian Couples
Impact of a Functional KIR2DS4 Allele on Heterosexual HIV-1 Transmission among Discordant Zambian Couples
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DOI：
10.1093/infdis/jiq075
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发表时间：
2011-02-15
影响因子：
6.4
通讯作者：
Kaslow, Richard A.
中科院分区：
文献类型：
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作者：
Merino, Aimee;Malhotra, Rakhi;Kaslow, Richard A.
杀伤细胞免疫球蛋白样受体（KIRs）及其人类白细胞抗原（HLA）配体相互作用以调节自然杀伤（NK）细胞功能。据报道，KIR基因含量和等位基因变异会影响人类免疫缺陷病毒（HIV）-1感染和发病机制。我们研究了KIR基因对赞比亚卢萨卡566对不一致夫妇中异性间HIV - 1传播的影响。KIR2DS4*001是已知的KIR2DS4中唯一编码功能性激活受体的等位基因，它与先证者（HIV - 1血清流行）伴侣中相对较高的HIV - 1病毒载量相关（β[标准误（SE）]，0.17[0.8]log₁₀；P = 0.04），并且与HIV - 1加速传播给同居的血清阴性伴侣相关（相对危险度[RH]，2.00；P = 0.004）。后一种关联与传播方向（男传女或女传男）、生殖器溃疡以及假定配体（HLA - Cw*04）的携带无关。在最初血清阴性的伴侣中，没有KIR基因变异与HIV - 1感染或血清转化后的早期病毒载量相关。对NK细胞功能的进一步分析应阐明KIR2DS4*001在HIV - 1传播中的作用。
Killer cell immunoglobulin-like receptors (KIRs) and their HLA ligands interact to regulate natural killer (NK) cell function. KIR gene content and allelic variations are reported to influence human immunodeficiency virus (HIV)-1 infection and pathogenesis. We investigated the impact of KIR genes on heterosexual HIV-1 transmission among 566 discordant couples from Lusaka, Zambia. KIR2DS4*001, the only allele of KIR2DS4 known to encode a functional activating receptor, was associated with relatively high viral load for HIV-1 in index (HIV-1 seroprevalent) partners (beta [standard error (SE)], .17 [.8] log(10); P = .04) and with accelerated transmission of HIV-1 to cohabiting seronegative partners (relative hazard [RH], 2.00; P = .004). The latter association was independent of the direction of transmission (male-to-female or female-to-male), genital ulcers, and carriage of the putative ligand (HLA-Cw*04). No KIR-gene variant in the initially seronegative partners was associated with HIV-1 acquisition or early viral load following seroconversion. Further analysis of NK cell function should clarify the role of KIR2DS4*001 in HIV-1 transmission.