Wiseman Roger W, Wojcechowskyj Jason A, Greene Justin M, Blasky Alex J, Gopon Tobias, Soma Taeko, Friedrich Thomas C, O'Connor Shelby L, O'Connor David H
Wisconsin National Primate Research Center, University of Wisconsin-Madison, 555 Science Drive, Madison, WI 53706, USA.
J Virol. 2007 Jan;81(1):349-61. doi: 10.1128/JVI.01841-06. Epub 2006 Oct 11.
Nonhuman primates are widely used to study correlates of protective immunity in AIDS research. Successful cellular immune responses have been difficult to identify because heterogeneity within macaque major histocompatibility complex (MHC) genes results in quantitative and qualitative differences in immune responses. Here we use microsatellite analysis to show that simian immunodeficiency virus (SIV)-susceptible cynomolgus macaques (Macaca fascicularis) from the Indian Ocean island of Mauritius have extremely simple MHC genetics, with six common haplotypes accounting for two-thirds of the MHC haplotypes in feral animals. Remarkably, 39% of Mauritian cynomolgus macaques carry at least one complete copy of the most frequent MHC haplotype, and 8% of these animals are homozygous. In stark contrast, entire MHC haplotypes are rarely conserved in unrelated Indian rhesus macaques. After intrarectal infection with highly pathogenic SIVmac239 virus, a pair of MHC-identical Mauritian cynomolgus macaques mounted concordant cellular immune responses comparable to those previously reported for a pair of monozygotic twins infected with the same strain of human immunodeficiency virus. Our identification of relatively abundant SIV-susceptible, MHC-identical macaques will facilitate research into protective cellular immunity.
在艾滋病研究中,非人灵长类动物被广泛用于研究保护性免疫的相关因素。由于猕猴主要组织相容性复合体(MHC)基因的异质性导致免疫反应在数量和质量上存在差异,因此难以识别成功的细胞免疫反应。在这里,我们使用微卫星分析表明,来自印度洋毛里求斯岛的易感染猿猴免疫缺陷病毒(SIV)的食蟹猕猴(Macaca fascicularis)具有极其简单的MHC遗传学,六种常见单倍型占野生食蟹猕猴MHC单倍型的三分之二。值得注意的是,39%的毛里求斯食蟹猕猴携带至少一个最常见MHC单倍型的完整拷贝,其中8%的动物是纯合子。与之形成鲜明对比的是,在不相关的印度恒河猴中,完整的MHC单倍型很少保守。在用高致病性SIVmac239病毒进行直肠内感染后,一对MHC相同的毛里求斯食蟹猕猴产生了与之前报道的一对感染相同株人类免疫缺陷病毒的同卵双胞胎相当的一致细胞免疫反应。我们对相对丰富的易感染SIV、MHC相同的猕猴的鉴定将有助于保护性细胞免疫的研究。