Frequent transmission of cytotoxic-T-lymphocyte escape mutants of human immunodeficiency virus type 1 in the highly HLA-A24-positive Japanese population.
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.
Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Tae
T
Furutsuki
Noriaki
N
Hosoya
Ai
A
Kawana-Tachikawa
Mariko
M
Tomizawa
Takashi
T
Odawara
Mieko
M
Goto
Yoshihiro
Y
Kitamura
Tetsuya
T
Nakamura
Anthony D
AD
Kelleher
David A
DA
Cooper
Aikichi
A
Iwamoto
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D003601:Cytotoxicity Tests, Immunologic; D018984:Epitopes, T-Lymphocyte; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000378:metabolism*; D059871:HLA-A24 Antigen; D006467:Hemophilia A / Q000150:complications; D006801:Humans; D016056:Immunodominant Epitopes; D007564:Japan / Q000453:epidemiology; D008297:Male; D008969:Molecular Sequence Data; D015229:Sexually Transmitted Diseases, Viral / Q000635:transmission / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D054311:nef Gene Products, Human Immunodeficiency Virus
D018984:Epitopes, T-Lymphocyte; D015693:Gene Products, nef; D015234:HLA-A Antigens; D059871:HLA-A24 Antigen; D016056:Immunodominant Epitopes; D054311:nef Gene Products, Human Immunodeficiency Virus