KIR3DL1 等位基因及其与人类白细胞抗原 I 类的上位性相互作用影响 Pumwani 性工作者队列中 HIV-1 获得的抗性和易感性。

KIR3DL1 alleles and their epistatic interactions with human leukocyte antigen class I influence resistance and susceptibility to HIV-1 acquisition in the Pumwani sex worker cohort.

机构信息

HIV and Host Genetics, National Microbiology Laboratory, Public Health Agency of Canada.

Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada.

出版信息

AIDS. 2018 Apr 24;32(7):841-850. doi: 10.1097/QAD.0000000000001735.

DOI:10.1097/QAD.0000000000001735

PMID:29280757

Abstract

OBJECTIVE

To determine the associations of KIR3DL1/S1(3DL1/S1) and its epistatic interactions with human leukocyte antigen class I (HLA-I) alleles with resistance and susceptibility to HIV-1.

DESIGN

Despite repeated exposure to HIV-1, a subset of women enrolled in the Pumwani sex worker cohort remain HIV uninfected. Previous studies have shown that specific HLA class I and II alleles were associated with this natural immunity. In this study, we investigated the association of 3DL1/S1 and its epistatic interactions with HLA-I, with resistance or susceptibility to HIV-1 acquisition.

METHODS

We used a sequence-based typing method to genotype 3DL1/S1 of 641 women in this cohort. The association of 3DL1/S1 and its epistatic interactions with HLA-I were analyzed using SPSS statistics software.

RESULTS

3DL1041 is enriched in the HIV-1-resistant women [P = 0.009, Pc = 0.0468, odds ratio (OR): 3.359, 95% confidence interval (CI): 1.39-8.32], whereas, 3DL1020 was associated with susceptibility to HIV-1 infection before correction for multiple comparisons (P = 0.029, Pc = 0.0858, OR: 0.316, 95%CI: 0.10-1.04). Epistatic interactions between several 3DL1 alleles and specific HLA-I alleles were observed. Among them the cocarriage of 3DL1041 with Bw4 (P = 1E - 05, Pc = 0.0015, OR: 13.33, 95%CI: 3.43-51.9), or Bw6 (P = 0.008, Pc = 0.272, OR: 3.92, 95%CI: 1.51-10.17), increased the odds of remaining HIV-1 uninfected. Further, 3DL1041+/Bw4+ women who entered the cohort HIV negative remained uninfected (P = 0.032, Pc = 0.0858). Cocarriage of 3DL101501 with C02 : 10 (P = 2.73E - 07, Pc = 7.0954E - 06), B15 : 03 (P = 3.21E - 04, Pc = 0.0042), A24 supertype (P = 8.89E - 04, Pc = 0.0077), or A23 : 01 (P = 0.0036, Pc = 0.0236) was associated with increased susceptibility to seroconversion.

CONCLUSION

The effects of interactions between 3DL1 and HLA-I alleles on resistance/susceptibility to HIV-1 infection suggest that innate immunity plays an important role in HIV-1 acquisition and should be studied and explored for HIV prevention.

摘要

目的

确定杀伤细胞免疫球蛋白样受体 3DL1/S1（3DL1/S1）及其与人类白细胞抗原 I 类（HLA-I）等位基因的上位性相互作用与 HIV-1 抵抗和易感性的关联。

设计

尽管反复接触 HIV-1，但参与 Pumwani 性工作者队列的一部分女性仍未感染 HIV。先前的研究表明，特定的 HLA Ⅰ类和Ⅱ类等位基因与这种天然免疫有关。在这项研究中，我们研究了 3DL1/S1 及其与 HLA-I 的上位性相互作用与 HIV-1 获得抵抗或易感性的关联。

方法

我们使用基于序列的分型方法对该队列中的 641 名女性的 3DL1/S1 进行基因分型。使用 SPSS 统计软件分析 3DL1/S1 及其上位性相互作用与 HLA-I 的关联。

结果

3DL1041 在 HIV-1 抵抗女性中更为丰富[P=0.009，Pc=0.0468，比值比（OR）：3.359，95%置信区间（CI）：1.39-8.32]，而 3DL1020 与 HIV-1 感染易感性相关，未经多次比较校正（P=0.029，Pc=0.0858，OR：0.316，95%CI：0.10-1.04）。观察到几个 3DL1 等位基因与特定 HLA-I 等位基因之间的上位性相互作用。其中，3DL1041 与 Bw4 的共携带（P=1E-05，Pc=0.0015，OR：13.33，95%CI：3.43-51.9）或 Bw6（P=0.008，Pc=0.272，OR：3.92，95%CI：1.51-10.17）增加了保持 HIV-1 未感染的几率。此外，3DL1041+/Bw4+的女性在进入队列时 HIV 阴性，仍保持未感染（P=0.032，Pc=0.0858）。3DL101501 与 C02:10（P=2.73E-07，Pc=7.0954E-06）、B15:03（P=3.21E-04，Pc=0.0042）、A24 超型（P=8.89E-04，Pc=0.0077）或 A23:01（P=0.0036，Pc=0.0236）的共携带与血清转换易感性增加相关。