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Journal of Virology, May 2008, p. 5093-5098, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02607-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Transmission of Simian Immunodeficiency Virus Carrying Multiple Cytotoxic T-Lymphocyte Escape Mutations with Diminished Replicative Ability Can Result in AIDS Progression in Rhesus Macaques{triangledown}

Sayuri Seki,1 Miki Kawada,1,2,3 Akiko Takeda,1 Hiroko Igarashi,2 Tetsutaro Sata,4 and Tetsuro Matano1,2,5,6*

International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-Ku, Tokyo 108-8639, Japan,1 Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-Ku, Tokyo 113-0033, Japan,2 Japanese Foundation for AIDS Prevention, 1-3-12 Misaki-cho, Chiyoda-Ku, Tokyo 101-0061, Japan,3 Department of Pathology, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan,4 AIDS Research Center, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8640, Japan,5 Tsukuba Primate Research Center, National Institute of Biomedical Innovation, 1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan6

Received 7 December 2007/ Accepted 3 March 2008

Cytotoxic T-lymphocyte (CTL) responses frequently select for immunodeficiency virus mutations that result in escape from CTL recognition with viral fitness costs. The replication in vivo of such viruses carrying not single but multiple escape mutations in the absence of the CTL pressure has remained undetermined. Here, we have examined the replication of simian immunodeficiency virus (SIV) with five gag mutations selected in a macaque possessing the major histocompatibility complex haplotype 90-120-Ia after its transmission into 90-120-Ia-negative macaques. Our results showed that even such a "crippled" SIV infection can result in persistent viral replication, multiple reversions, and AIDS progression.

* Corresponding author. Mailing address: International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Phone: 81-3-6409-2078. Fax: 81-3-6409-2076. E-mail: matano{at}m.u-tokyo.ac.jp

{triangledown} Published ahead of print on 12 March 2008.

Journal of Virology, May 2008, p. 5093-5098, Vol. 82, No. 10
0022-538X/08/$08.00+0     doi:10.1128/JVI.02607-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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