The Major Genetic Determinants of HIV-1 Control Affect HLA Class I Peptide Presentation

TLDR

Approximately 1 in 300 HIV‑infected individuals are long‑term controllers who suppress the virus without therapy and avoid AIDS. The study aims to uncover the genetic basis for HIV control. Genome‑wide analysis identified over 300 significant variants in the HLA region, with six key amino‑acid residues—five in the peptide‑binding groove—suggesting that HLA‑mediated peptide binding differences drive the genetic disparity between controllers and progressors. Pereyra et al.

Abstract

Getting HIV Under Control Approximately 1 in 300 people infected with HIV are HIV “controllers” who are able to maintain long-term control of the virus without medication and who do not progress to AIDS. Uncovering the genetic basis for this ability is of great interest. Pereyra et al. (p. 1551 , published online 4 November; see the Perspective by McMichael and Jones ) now present genome-wide association results from patients enrolled in the International HIV Controllers Study. The analysis compared HIV controllers of European, African-American, and Hispanic descent with HIV progressors and found >300 variants that reached genome-wide significance, all of which were in the major histocompatibility class I (HLA) region on chromosome 6. Analysis of the effects of individual amino acids within classical HLA proteins revealed six independently significant residues, five of which lined the peptide-binding groove. Thus, differences in binding to viral peptide antigens by HLA may be the major factors underlying genetic differences between HIV controllers and progressors.