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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

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
Externally publishedYes

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).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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