HLA-B 信号肽多态性影响 HIV-1 的获得率，但不影响病毒载量。
HLA-B signal peptide polymorphism influences the rate of HIV-1 acquisition but not viral load.
机构信息
Department of Medicine, University of Alabama at Birmingham, AL 35294-0022, USA.
出版信息
J Infect Dis. 2012 Jun 15;205(12):1797-805. doi: 10.1093/infdis/jis275. Epub 2012 Apr 5.
Abstract
Human leukocyte antigen alleles influence the immune response to HIV-1. Signal peptides cleaved from those alleles bind to HLA-E and mediate natural killer cell function. Signal peptides of HLA-A and HLA-C proteins carry methionine (Met) at anchor position 2 (P2); those of HLA-B carry Met or threonine (Thr). Different P2 residues alter HLA-E binding to its cognate receptors and may impact HIV-1 acquisition. Among Zambian couples (N = 566) serodiscordant for HIV-1, P2-Met accelerated acquisition in the HIV-1-negative partner (relative hazard [RH], 1.79). Among seroconverting Zambian (n = 240) and Rwandan (n = 64) partners, P2-Met also accelerated acquisition (RH, 1.47 and RH, 1.83 respectively). HLA-B alleles displaying the reportedly protective Bw4 epitope carry P2-Thr. Bw4/P2-Thr and Bw6/P2-Thr showed similar protective effects compared with Bw6/P2-Met. Neither motif was associated with viral load. The influence of HLA-B alleles on HIV/AIDS may derive from multiple motifs in and beyond the mature proteins.
摘要
人类白细胞抗原等位基因影响 HIV-1 的免疫反应。从这些等位基因中切割出来的信号肽与 HLA-E 结合并介导自然杀伤细胞功能。HLA-A 和 HLA-C 蛋白的信号肽在锚定位置 2 (P2) 携带蛋氨酸 (Met)；HLA-B 的信号肽携带 Met 或苏氨酸 (Thr)。不同的 P2 残基改变了 HLA-E 与其同源受体的结合，可能会影响 HIV-1 的获得。在感染 HIV-1 血清学不一致的赞比亚夫妇中（N=566），P2-Met 加速了 HIV-1 阴性伴侣的获得（相对危险度 [RH]，1.79）。在赞比亚（n=240）和卢旺达（n=64）血清转换的伴侣中，P2-Met 也加速了获得（RH，1.47 和 RH，1.83）。报道具有保护作用的 Bw4 表位的 HLA-B 等位基因携带 P2-Thr。Bw4/P2-Thr 和 Bw6/P2-Thr 与 Bw6/P2-Met 具有相似的保护作用。这两个基序均与病毒载量无关。HLA-B 等位基因对 HIV/AIDS 的影响可能来自于成熟蛋白内外的多个基序。
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