HLA-B signal peptide polymorphism influences the rate of HIV-1 acquisition but not viral load

Aimee M. Merino, Wei Song, Dongning He, Joseph Mulenga, Susan Allen, Eric Hunter, Jianming Tang, Richard A. Kaslow

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1797-1805
Number of pages9
JournalJournal of Infectious Diseases
Volume205
Issue number12
DOIs
StatePublished - Jun 15 2012

Bibliographical note

Funding Information:
Financial Support. This work was supported by the National Institute of Allergy and Infectious Diseases (grants R01 AI071906 and R01 AI064060 to R. A. K. and E. H., respectively).

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