Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, 2288 GJ Rijswijk, The Netherlands.
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15175-80. doi: 10.1073/pnas.1009136107. Epub 2010 Aug 9.
In the absence of treatment, most HIV-1-infected humans develop AIDS. However, a minority are long-term nonprogressors, and resistance is associated with the presence of particular HLA-B27/B57 molecules. In contrast, most HIV-1-infected chimpanzees do not contract AIDS. In comparison with humans, chimpanzees experienced an ancient selective sweep affecting the MHC class I repertoire. We have determined the peptide-binding properties of frequent chimpanzee MHC class I molecules, and show that, like HLA-B27/B57, they target similar conserved areas of HIV-1/SIV(cpz). In addition, many animals appear to possess multiple molecules targeting various conserved areas of the HIV-1/SIV(cpz) Gag protein, a quantitative aspect of the immune response that may further minimize the chance of viral escape. The functional characteristics of the contemporary chimpanzee MHC repertoire suggest that the selective sweep was caused by a lentiviral pandemic.
在缺乏治疗的情况下,大多数感染 HIV-1 的人类会发展为艾滋病。然而,少数人是长期非进展者,而耐药性与存在特定的 HLA-B27/B57 分子有关。相比之下,大多数感染 HIV-1 的黑猩猩不会患上艾滋病。与人类相比,黑猩猩经历了一次古老的选择性清扫,影响了 MHC Ⅰ类的基因库。我们已经确定了常见的黑猩猩 MHC Ⅰ类分子的肽结合特性,并表明它们与 HLA-B27/B57 一样,针对 HIV-1/SIV(cpz)的相似保守区域。此外,许多动物似乎拥有多种针对 HIV-1/SIV(cpz)Gag 蛋白不同保守区域的分子,这是免疫反应的一个定量方面,可能进一步降低病毒逃逸的机会。当代黑猩猩 MHC 基因库的功能特征表明,这种选择性清扫是由慢病毒大流行引起的。