自然杀伤细胞介导的固有筛检效应在 HIV-1 中的作用：KIR/HLA 多态性对东非 HIV-1 亚型特异性获得的影响。
Natural killer cell-mediated innate sieve effect on HIV-1: the impact of KIR/HLA polymorphism on HIV-1 subtype-specific acquisition in east Africa.
机构信息
US Military HIV Research Program.
出版信息
J Infect Dis. 2013 Oct 15;208(8):1250-4. doi: 10.1093/infdis/jit349. Epub 2013 Aug 6.
Abstract
Here we explore the association between killer cell immunoglobulin-like receptor (KIR)/HLA and human immunodeficiency virus type 1 (HIV-1) acquisition with different viral subtypes circulating in East Africa. In the prospective Cohort Development (CODE) cohort (Mbeya, Tanzania), carriers of KIR3DS1 and its putative ligand (HLA-A or HLA-B Bw4-80Ile alleles) showed increased HIV-1 acquisition risk (odds ratio [OR] = 3.46; 95% confidence interval [CI], 1.12-10.63; P = .04) and a trend for enrichment for subtype A and A-containing recombinants (78% vs. 46%; OR = 4.05; 95% CI, .91-28.30; P = .09) at the expense of subtype C (11% vs. 43%; OR = 0.17; 95% CI, .01-.97; P = .08). In vitro, only natural killer cells from KIR3DS1(+)/HLA-Bw4-80Ile(+) healthy donors showed a 2-fold increased capacity to inhibit replication of subtype C vs subtype A viruses (P = .01). These findings suggest the presence of an innate sieve effect and may inform HIV-1 vaccine development.
摘要
在这里，我们探讨了在东非流行的不同病毒亚型中，杀伤细胞免疫球蛋白样受体 (KIR)/HLA 与人类免疫缺陷病毒 1 型 (HIV-1) 获得之间的关联。在前瞻性队列发展 (CODE) 队列 (坦桑尼亚姆贝亚) 中，KIR3DS1 及其假定配体（HLA-A 或 HLA-B Bw4-80Ile 等位基因）的携带者显示出 HIV-1 获得风险增加（优势比 [OR] = 3.46；95%置信区间 [CI]，1.12-10.63；P =.04），并且 A 亚型和包含 A 的重组体的富集趋势明显（78%比 46%；OR = 4.05；95%CI，.91-28.30；P =.09），而 C 亚型的比例降低（11%比 43%；OR = 0.17；95%CI，.01-.97；P =.08）。在体外，只有 KIR3DS1(+)/HLA-Bw4-80Ile(+) 健康供体的自然杀伤细胞显示出对 C 亚型病毒复制的抑制能力增加了 2 倍，而对 A 亚型病毒的抑制能力没有增加（P =.01）。这些发现表明存在先天筛检效应，可能为 HIV-1 疫苗的开发提供信息。
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