en
Scientific article
English

Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression

Published inJournal of virology, vol. 81, no. 12, p. 6742-6751
Publication date2007
Abstract

The possession of some HLA class I molecules is associated with delayed progression to AIDS. The mechanism behind this beneficial effect is unclear. We tested the idea that cytotoxic T-cell responses restricted by advantageous HLA class I molecules impose stronger selection pressures than those restricted by other HLA class I alleles. As a measure of the selection pressure imposed by HLA class I alleles, we determined the extent of HLA class I-associated epitope variation in a cohort of European human immunodeficiency virus (HIV)-positive individuals (n=84). We validated our findings in a second, distinct cohort of African patients (n=516). We found that key HIV epitopes restricted by advantageous HLA molecules (B27, B57, and B51 in European patients and B5703, B5801, and B8101 in African patients) were more frequently mutated in individuals bearing the restricting HLA than in those who lacked the restricting HLA class I molecule. HLA alleles associated with clinical benefit restricted certain epitopes for which the consensus peptides were frequently recognized by the immune response despite the circulating virus's being highly polymorphic. We found a significant inverse correlation between the HLA-associated hazard of disease progression and the mean HLA-associated prevalence of mutations within epitopes (P=0.028; R2=0.34). We conclude that beneficial HLA class I alleles impose strong selection at key epitopes. This is revealed by the frequent association between effective T-cell responses and circulating viral escape mutants and the rarity of these variants in patients who lack these favorable HLA class I molecules, suggesting a significant pressure to revert.

Keywords
  • Africa
  • Alleles
  • Cohort Studies
  • Disease Progression
  • Epitopes/chemistry
  • Genes, MHC Class I
  • Genes, Viral
  • HIV/ genetics
  • HIV Infections/ blood/ genetics/virology
  • Humans
  • Leukocytes, Mononuclear/virology
  • Mutation
  • Spain
  • Switzerland
  • T-Lymphocytes/ immunology/ virology
Citation (ISO format)
FRATER, A. John et al. Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression. In: Journal of virology, 2007, vol. 81, n° 12, p. 6742–6751. doi: 10.1128/JVI.00022-07
Main files (1)
Article
accessLevelRestricted
Identifiers
ISSN of the journal0022-538X
483views
0downloads

Technical informations

Creation21.06.2010 10:24:13
First validation21.06.2010 10:24:13
Update time14.03.2023 15:43:39
Status update14.03.2023 15:43:39
Last indexation12.02.2024 18:29:58
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack