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Journal of Virology, December 2002, p. 12845-12854, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12845-12854.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mamu-A*01 Allele-Mediated Attenuation of Disease Progression in Simian-Human Immunodeficiency Virus Infection

Zhi-Qiang Zhang,* Tong-Ming Fu, Danilo R. Casimiro, Mary-Ellen Davies, Xiaoping Liang, William A. Schleif, Larry Handt, Lynda Tussey, Minchun Chen, Aimin Tang, Keith A. Wilson, Wendy L. Trigona, Daniel C. Freed, Charles Y. Tan, Melanie Horton, Emilio A. Emini, and John W. Shiver

Merck Research Laboratories, West Point, Pennsylvania 19486

Received 5 July 2002/ Accepted 5 September 2002

Expression of several major histocompatibility complex (MHC) class I alleles is associated with a protective effect against disease progression in both human immunodeficiency virus type 1 and simian immunodeficiency virus infection. To understand the mechanism underlying this effect, we investigated the expression of the MHC class I allele Mamu-A*01 in simian-human immunodeficiency virus (SHIV) infection, one of the major models for evaluation of AIDS vaccine candidates. We found that disease progression was significantly delayed in Mamu-A*01-positive rhesus monkeys infected with the highly pathogenic SHIV 89.6P. The delay corresponded not only to a noted Mamu-A*01-restricted dominant cytotoxic T-lymphocyte (CTL) response but also to a lower viral load in lymph nodes (LN) and, importantly, to minimal destruction of LN structure during early infection. In contrast, Mamu-A*01-negative monkeys exhibited massive destruction of LN structure with accompanying rapid disease progression. These data indicate that MHC class I allele-restricted CTL responses may play an important role in preservation of lymphoid tissue structure, thereby resulting in attenuation of disease progression in immunodeficiency virus infection.

* Corresponding author. Mailing address: Department of Viral Vaccine Research, Merck Research Laboratories, 770 Sumneytown Pike, P.O. Box 4, WP16-225, West Point, PA 19486. Phone: (215) 652-2718. Fax: (215) 652-7320. E-mail: zhiqiang_zhang{at}merck.com.

Journal of Virology, December 2002, p. 12845-12854, Vol. 76, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.24.12845-12854.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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