CD8 T-cell recognition of multiple epitopes within specific Gag regions is associated with maintenance of a low steady-state viremia in human immunodeficiency virus type 1-seropositive patients

J Virol. 2007 Mar;81(5):2440-8. doi: 10.1128/JVI.01847-06. Epub 2006 Dec 20.

Abstract

The importance of HLA class I-restricted CD8 T-cell responses in the control of human immunodeficiency virus (HIV) infection is generally accepted. While several studies have shown an association of certain HLA class I alleles with slower disease progression, it is not fully established whether this effect is mediated by HIV-specific CD8 T-cell responses restricted by these alleles. In order to study the influence of the HLA class I alleles on the HIV-specific CD8 T-cell response and on viral control, we have assessed HIV-specific epitope recognition, plasma viral load, and expression of HLA class I alleles in a cohort of HIV-seropositive bar workers. Possession of the HLA class I alleles B5801, B8101, and B0702 was associated with a low median viral load and simultaneously with a broader median recognition of Gag epitopes compared to all other HLA alleles (twofold increase) (P = 0.0035). We further found an inverse linear relationship between the number of Gag epitopes recognized and the plasma viral load (R = -0.36; P = 0.0016). Particularly, recognition of multiple epitopes within two regions of Gag (amino acids [aa] 1 to 75 and aa 248 to 500) was associated with the maintenance of a low steady-state viremia, even years after acute infection.

Publication types

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

MeSH terms

  • CD8-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Gene Products, gag / genetics
  • Gene Products, gag / immunology*
  • Genes, MHC Class I
  • HIV Seropositivity / genetics
  • HIV Seropositivity / immunology*
  • HIV Seropositivity / virology*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / physiology
  • Humans
  • Viremia / immunology
  • Viremia / virology
  • Virus Replication

Substances

  • Epitopes
  • Gene Products, gag