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Journal of Virology, August 2004, p. 8437-8445, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8437-8445.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Frequent Transmission of Cytotoxic-T-Lymphocyte Escape Mutants of Human Immunodeficiency Virus Type 1 in the Highly HLA-A24-Positive Japanese Population

Tae Furutsuki,1,2,{dagger} Noriaki Hosoya,1,{dagger} Ai Kawana-Tachikawa,1,{dagger} Mariko Tomizawa,1 Takashi Odawara,3 Mieko Goto,1 Yoshihiro Kitamura,1 Tetsuya Nakamura,3 Anthony D. Kelleher,4 David A. Cooper,4 and Aikichi Iwamoto1,3*

Division of Infectious Diseases, Advanced Clinical Research Center, Department of Infectious Diseases and Applied Immunology, Research Hospital,1 Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639,3 Department of Applied Biochemistry, Tokai University, Hiratsuka-shi, Kanagawa, Japan,2 National Centre in HIV Epidemiology and Clinical Research, University of New South Wales, Sydney, Australia4

Received 5 January 2004/ Accepted 30 March 2004

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.

* Corresponding author. Mailing address: 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. Phone: 81-3-5449-5359. Fax: 81-3-54495427. E-mail: aikichi{at}ims.u-tokyo.ac.jp.

{dagger} T.F., N.H., and A.K.-T. contributed equally to this work.

Journal of Virology, August 2004, p. 8437-8445, Vol. 78, No. 16
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.16.8437-8445.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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