Association of Major Histocompatibility Complex Class I Haplotypes with Disease Progression after Simian Immunodeficiency Virus Challenge in Burmese Rhesus Macaques

作者：Nomura Takushi; Yamamoto Hiroyuki; Shiino Teiichiro; Takahashi Naofumi; Nakane Taku; Iwamoto Nami; Ishii Hiroshi; Tsukamoto Tetsuo; Kawada Miki; Matsuoka Saori; Takeda Akiko; Terahara Kazutaka; Tsunetsugu Yokota Yasuko; Iwata Yoshikawa Naoko; Hasegawa Hideki; Sata Tetsutaro; Naruse Taeko K; Kimura Akinori; Matano Tetsuro^*

来源：Journal of Virology, 2012, 86(12): 6481-6490.

DOI：10.1128/JVI.07077-11

Nonhuman primate AIDS models are essential for the analysis of AIDS pathogenesis and the evaluation of vaccine efficacy. Multiple studies on human immunodeficiency virus and simian immunodeficiency virus (SIV) infection have indicated the association of major histocompatibility complex class I (MHC-I) genotypes with rapid or slow AIDS progression. The accumulation of macaque groups that share not only a single MHC-I allele but also an MHC-I haplotype consisting of multiple polymorphic MHC-I loci would greatly contribute to the progress of AIDS research. Here, we investigated SIVmac239 infections in four groups of Burmese rhesus macaques sharing individual MHC-I haplotypes, referred to as A, E, B, and J. Out of 20 macaques belonging to A(+) (n = 6), E+ (n = 6), B+ (n = 4), and J(+) (n = 4) groups, 18 showed persistent viremia. Fifteen of them developed AIDS in 0.5 to 4 years, with the remaining three at 1 or 2 years under observation. A(+) animals, including two controllers, showed slower disease progression, whereas J(+) animals exhibited rapid progression. E+ and B+ animals showed intermediate plasma viral loads and survival periods. Gag-specific CD8(+) T-cell responses were efficiently induced in A(+) animals, while Nef-specific CD8(+) T-cell responses were in A(+), E+, and B+ animals. Multiple comparisons among these groups revealed significant differences in survival periods, peripheral CD4(+) T-cell decline, and SLY-specific CD4(+) T-cell polyfunctionality in the chronic phase. This study indicates the association of MHC-I haplotypes with AIDS progression and presents an AIDS model facilitating the analysis of virus-host immune interaction.

• 出版日期2012-6
• 单位河北医科大学