The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Academic Article

Abstract

  • Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.
  • Published In

  • Science  Journal
  • Keywords

  • African Americans, Alleles, Amino Acids, Antigen Presentation, CD8-Positive T-Lymphocytes, Cohort Studies, Disease Progression, European Continental Ancestry Group, Genes, MHC Class I, Genome-Wide Association Study, HIV Antigens, HIV Infections, HIV Long-Term Survivors, HIV-1, HLA-A Antigens, HLA-B Antigens, HLA-C Antigens, Haplotypes, Hispanic Americans, Humans, Immunity, Innate, Logistic Models, Models, Molecular, Polymorphism, Single Nucleotide, Protein Conformation, Viral Load
  • Digital Object Identifier (doi)

    Author List

  • International HIV Controllers Study; Pereyra F; Jia X; McLaren PJ; Telenti A; de Bakker PIW; Walker BD; Ripke S; Brumme CJ; Pulit SL
  • Start Page

  • 1551
  • End Page

  • 1557
  • Volume

  • 330
  • Issue

  • 6010