HIV evolution: CTL escape mutation and reversion after transmission

Nat Med. 2004 Mar;10(3):282-9. doi: 10.1038/nm992. Epub 2004 Feb 8.


Within-patient HIV evolution reflects the strong selection pressure driving viral escape from cytotoxic T-lymphocyte (CTL) recognition. Whether this intrapatient accumulation of escape mutations translates into HIV evolution at the population level has not been evaluated. We studied over 300 patients drawn from the B- and C-clade epidemics, focusing on human leukocyte antigen (HLA) alleles HLA-B57 and HLA-B5801, which are associated with long-term HIV control and are therefore likely to exert strong selection pressure on the virus. The CTL response dominating acute infection in HLA-B57/5801-positive subjects drove positive selection of an escape mutation that reverted to wild-type after transmission to HLA-B57/5801-negative individuals. A second escape mutation within the epitope, by contrast, was maintained after transmission. These data show that the process of accumulation of escape mutations within HIV is not inevitable. Complex epitope- and residue-specific selection forces, including CTL-mediated positive selection pressure and virus-mediated purifying selection, operate in tandem to shape HIV evolution at the population level.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Child
  • Epitopes
  • Evolution, Molecular*
  • Female
  • Genetic Variation
  • HIV Infections / immunology
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / physiology*
  • HLA-B Antigens / genetics
  • HLA-B Antigens / immunology
  • Humans
  • Infectious Disease Transmission, Vertical
  • Likelihood Functions
  • Mutation*
  • Phylogeny
  • Selection, Genetic
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Viral Load


  • Epitopes
  • HLA-B Antigens
  • HLA-B57 antigen