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

ZQ Zhang, TM Fu, DR Casimiro, ME Davies… - Journal of …, 2002 - Am Soc Microbiol
ZQ Zhang, TM Fu, DR Casimiro, ME Davies, X Liang, WA Schleif, L Handt, L Tussey…
Journal of virology, 2002Am Soc Microbiol
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 …
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.
American Society for Microbiology