Immunogenetic factors in early immune control of human immunodeficiency virus type 1 (HIV-1) infection: Evaluation of HLA class I amino acid variants in two African populations

• Type of Material: Article
• Authors: Howard W. Wiener, University of Alabama Birmingham; Sadeep Shrestha, University of Alabama Birmingham; Hailin Lu, University of Alabama Birmingham; Etienne Karita, Project San Francisco; William Kilembe, Zambia Emory HIV Research Project; Susan Allen, Emory University; Eric Hunter, Emory University; Paul A. Goepfert, University of Alabama Birmingham; Jianming Tang, University of Alabama Birmingham
• Language: English
• Date: 2018-03-01
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 American Society for Histocompatibility and Immunogenetics
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.humimm.2017.12.005
• Title of Journal or Parent Work: Human Immunology
• ISSN: 0198-8859
• Volume: 79
• Issue: 3
• Start Page: 166
• End Page: 171
• Grant/Funding Information: This work was funded primarily by the United States National Institute of Allergy and Infectious Diseases (NIAID), through two R01 grants (AI071906 to J.T. and AI064060 to P.A.G/E.H./J.T.).
• Keywords: Viral load; Antigen presentation; Africa; Motifs; RHEUMATOID-ARTHRITIS; VIRAL LOAD; ASSOCIATION; Immunity; Science & Technology; ALLELES; HOST GENETICS; LINKAGE DISEQUILIBRIUM; Life Sciences & Biomedicine; HIV-1; DYNAMICS; TRANSMISSION; EXTENDED HUMAN MHC; HLA-I; DISEASE PROGRESSION; Immunology
• Research Categories: Health Sciences, Epidemiology; Health Sciences, Pathology; Health Sciences, Immunology

Abstract

Immune control of HIV-1 infection depends heavily on cytotoxic T-lymphocyte responses restricted by diverse HLA class I molecules. Recent work has uncovered specific amino acid residues (AARs) that seem to dictate the extent of immune control in African Americans, which prompted us to test these emerging hypotheses in seroconverters (SCs) from southern and eastern Africa. Based on data from 196 Zambians and 76 Rwandans with fully resolved HLA alleles and pre-therapy HIV-1 viral loads (VL) in the first 3- to 36-month of infection (>2300 person-visits), four AARs of primary interest (positions 63, 97, 116 and 245 in the mature HLA-B protein) were found to explain 8.1% and 15.8% of variance in set-point VL for these cohorts (P =.024 and 7.5 × 10 −6 , respectively). Two AARs not reported previously (167S in HLA-B and 116F in HLA-C) also showed relatively consistent associations with VL (adjusted P =.009–.069), while many population-specific associations were also noted (false discovery rate <0.05). Extensive and often strong linkage disequilibrium among neighboring AAR variants called for more extensive analyses of AAR haplotypes in diverse cohorts before the structural basis of antigen presentation can be fully comprehended.