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Frequent transmission of cytotoxic-T-lymphocyte escape mutants of human immunodeficiency virus type 1 in the highly HLA-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.
Journal of Virology (Impact Factor: 4.65). 08/2004; 78(16):8437-45. DOI: 10.1128/JVI.78.16.8437-8445.2004
Source: PubMed

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.

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    • "ith es - cape from CTL epitopes restricted by these common HLA alleles . Such studies include HLA - B57 positive individ - uals in South Africa , HLA - A24 expression subjects in the Japanese population and others that have been used to track potential CTL epitopes by reverse genetic approaches [ Allen et al . , 2004 ; de Oliveira et al . , 2004 ; Furutsuki et al . , 2004 ; Leslie et al . , 2005 ] . Furthermore , in a recent work from our laboratory , population wide adaptation may even have rendered an HLA allele , in this case HLA - B * 1503 , from being associated with reduced viral load in a popu - lation with low allele frequency to a an allele associated with higher than average viral load in the p"
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