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.

Figure 1.

Kaplan–Meier plot showing human immunodeficiency virus type 1 (HIV-1) acquisition-free time in nonindex partners with position 2 (P2)- threonine (Thr)/P2-Thr, P2- methionine (Met)/P2-Thr, and P2-Met/P2-Met genotypes. For the Wilcoxon test, P = .004, and for the log-rank test, P = .01. The summary table shows numbers of acquisition-free couples at various follow-up intervals. Plots shown represent relative occurrence among those with the factors of interest, not overall incidence in the population. Rates of acquisition depicted here in discordant couples selected for risk characteristics are higher than rates in the entire discordant couple cohort.