Compensatory mutation partially restores fitness and delays reversion of escape mutation within the immunodominant HLA-B*5703-restricted Gag epitope in chronic human immunodeficiency virus type 1 infection

J Virol. 2007 Aug;81(15):8346-51. doi: 10.1128/JVI.00465-07. Epub 2007 May 16.

Abstract

HLA-B*5703 is associated with effective immune control in human immunodeficiency virus type 1 (HIV-1) infection. Here we describe an escape mutation within the immunodominant HLA-B*5703-restricted epitope in chronic HIV-1 infection, KAFSPEVIPMF (Gag 162-172), and demonstrate that this mutation reduces viral replicative capacity. Reversion of this mutation following transmission to HLA-B*5703-negative recipients was delayed by the compensatory mutation S165N within the same epitope. These data may help explain the observed association between HLA-B*5703 and long-term control of viremia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Gene Products, gag / classification
  • Gene Products, gag / genetics
  • Gene Products, gag / immunology*
  • HIV Infections / immunology*
  • HIV-1 / genetics
  • HIV-1 / metabolism*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology*
  • Humans
  • Immunodominant Epitopes*
  • Likelihood Functions
  • Mutation*
  • Phylogeny
  • Virus Replication

Substances

  • Gene Products, gag
  • HLA-B Antigens
  • Immunodominant Epitopes