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. (24th April 2018)

• Record Type: Journal Article
• Authors: Luo, Ma; Czarnecki, Chris; Nebroski, Michelle; Kimani, Joshua; Bernard, Nicole; Plummer, Francis A.
• Is Part Of: AIDS. Volume 32:Number 7(2018)
• Publication Date: 2018-04-24
• Subjects: A*23 : 01 -- B*15 : 03 -- Bw4 and Bw6 -- C*02 : 10 -- HIV-resistant female sex workers in Nairobi -- KIR3DL1 and human leukocyte antigen class I epistatic interactions -- KIR3DL1*01501 -- KIR3DL1*020 -- KIR3DL1*041 -- resistance or susceptibility to HIV acquisition; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001735
• Languages: English
• ISSNs: 0269-9370

Abstract

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: 3DL1 * 041 is enriched in the HIV-1-resistant women [ P = 0.009, P c = 0.0468, odds ratio (OR): 3.359, 95% confidence interval (CI): 1.39–8.32], whereas, 3DL1 * 020 was associated with susceptibility to HIV-1 infection before correction for multiple comparisons ( P = 0.029, P c = 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 3DL1 * 041 with Bw4 ( P = 1E − 05, P c = 0.0015, OR: 13.33, 95%CI: 3.43–51.9), or Bw6 ( P = 0.008, P c = 0.272, OR: 3.92, 95%CI: 1.51–10.17), increased the odds of remaining HIV-1 uninfected. Further, 3DL1 * 041+/Bw4+ women who entered the cohort HIV negative remained uninfected ( P = 0.032, P c = 0.0858). Cocarriage of 3DL1 * 01501 with C * 02 : 10 ( P = 2.73E − 07, P c = 7.0954E − 06), B * 15 : 03 ( P = 3.21E − 04, P c = 0.0042), A24 supertype ( P = 8.89E − 04, P c = 0.0077), or A * 23 : 01 ( P = 0.0036, P c = 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. Abstract : Supplemental Digital Content is available in the text