Mamu-A*01 Allele-Mediated Attenuation of Disease Progression in Simian-Human Immunodeficiency Virus Infection
Open Access
- 15 December 2002
- journal article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 76 (24), 12845-12854
- https://doi.org/10.1128/jvi.76.24.12845-12854.2002
Abstract
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.Keywords
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