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

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.