title: HLA-B signal peptide polymorphism influences the rate of HIV-1 acquisition but not viral load.
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.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, AL 35294-0022, USA.
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Merino
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Dongning
authors.initials: D
authors.lastname: He
authors.forename: Joseph
authors.initials: J
authors.lastname: Mulenga
authors.forename: Susan
authors.initials: S
authors.lastname: Allen
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D015796:HLA-B27 Antigen / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D021382:Protein Sorting Signals; D012432:Rwanda; D019562:Viral Load; D015024:Zambia
chemical_list: C090660:HLA-B protein, human; D015796:HLA-B27 Antigen; D021382:Protein Sorting Signals