Frequent transmission of cytotoxic-T-lymphocyte escape mutants of human immunodeficiency virus type 1 in the highly HLA-A24-positive Japanese population.
PMID 15280452 · Journal of virology · 2004 · DOI 10.1128/JVI.78.16.8437-8445.2004
Authors: Tae Furutsuki; Noriaki Hosoya; Ai Kawana-Tachikawa; Mariko Tomizawa; Takashi Odawara; Mieko Goto; Yoshihiro Kitamura; Tetsuya Nakamura; Anthony D Kelleher; David A Cooper; Aikichi Iwamoto
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.
Amino Acid Sequence; Amino Acid Substitution; Cytotoxicity Tests, Immunologic; Epitopes, T-Lymphocyte; Gene Products, nef; HIV Infections; HIV-1; HLA-A Antigens; HLA-A24 Antigen; Hemophilia A; Humans; Immunodominant Epitopes; Japan; Male; Molecular Sequence Data; Sexually Transmitted Diseases, Viral; T-Lymphocytes, Cytotoxic; nef Gene Products, Human Immunodeficiency Virus
Cite
Tae Furutsuki; Noriaki Hosoya; Ai Kawana-Tachikawa; Mariko Tomizawa; Takashi Odawara; Mieko Goto; Yoshihiro Kitamura; Tetsuya Nakamura; Anthony D Kelleher; David A Cooper; Aikichi Iwamoto. Frequent transmission of cytotoxic-T-lymphocyte escape mutants of human immunodeficiency virus type 1 in the highly HLA-A24-positive Japanese population. Journal of virology (2004). PMID 15280452. DOI 10.1128/JVI.78.16.8437-8445.2004.