Frequent transmission of cytotoxic-T-lymphocyte escape mutants of human immunodeficiency virus type 1 in the highly HLA-A24-positive Japanese population

J Virol. 2004 Aug;78(16):8437-45. doi: 10.1128/JVI.78.16.8437-8445.2004.

Abstract

Although Japan is classified as a country with a low prevalence of human immunodeficiency virus type 1 (HIV-1), domestic sexual transmission has been increasing steadily. Because 70% of the Japanese population expresses HLA-A24 (genotype HLA-A*2402), we wished to assess the effect of the dominant HLA type on the evolution and transmission of HIV-1 among the Japanese population. Twenty-three out of 25 A24-positive Japanese patients had a Y-to-F substitution at the second position [Nef138-10(2F)] in an immunodominant A24-restricted CTL epitope in their HIV-1 nef gene (Nef138-10). None of 12 A24-negative Japanese hemophiliacs but 9 out of 16 patients infected through unprotected sexual intercourse had Nef138-10(2F) (P < 0.01). Two of two A24-positive but none of six A24-negative Australians had Nef138-10(2F). Nef138-10(2F) peptides bound well to the HLA-A*2402 heavy chain; however, Nef138-10(2F) was expressed poorly on the cell surface from the native protein. Thus, HIV-1 with Nef138-10(2F) appears to be a cytotoxic-T-lymphocyte escape mutant and has been transmitted frequently by sexual contact among the highly A24-positive Japanese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution*
  • Cytotoxicity Tests, Immunologic
  • Epitopes, T-Lymphocyte
  • Gene Products, nef / chemistry
  • Gene Products, nef / genetics
  • Gene Products, nef / immunology
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HLA-A Antigens / metabolism*
  • HLA-A24 Antigen
  • Hemophilia A / complications
  • Humans
  • Immunodominant Epitopes
  • Japan / epidemiology
  • Male
  • Molecular Sequence Data
  • Sexually Transmitted Diseases, Viral / transmission
  • Sexually Transmitted Diseases, Viral / virology
  • T-Lymphocytes, Cytotoxic / immunology*
  • nef Gene Products, Human Immunodeficiency Virus

Substances

  • Epitopes, T-Lymphocyte
  • Gene Products, nef
  • HLA-A Antigens
  • HLA-A24 Antigen
  • Immunodominant Epitopes
  • nef Gene Products, Human Immunodeficiency Virus