Institut de Génétique Humaine, Centre National de la Recherche Scientifique, Unité Propre de Recherche 1142, Laboratoires de Virologie Moléculaire, 34000 Montpellier, France.
Cell Host Microbe. 2012 Feb 16;11(2):205-17. doi: 10.1016/j.chom.2012.01.007. Epub 2012 Feb 1.
SAMHD1 has recently been identified as an HIV-1 restriction factor operating in myeloid cells. As a countermeasure, the Vpx accessory protein from HIV-2 and certain lineages of SIV have evolved to antagonize SAMHD1 by inducing its ubiquitin-proteasome-dependent degradation. Here, we show that SAMHD1 experienced strong positive selection episodes during primate evolution that occurred in the Catarrhini ancestral branch prior to the separation between hominoids (gibbons and great apes) and Old World monkeys. The identification of SAMHD1 residues under positive selection led to mapping the Vpx-interaction domain of SAMHD1 to its C-terminal region. Importantly, we found that while SAMHD1 restriction activity toward HIV-1 is evolutionarily maintained, antagonism of SAMHD1 by Vpx is species-specific. The distinct evolutionary signature of SAMHD1 sheds light on the development of its antiviral specificity.
SAMHD1 最近被鉴定为一种在髓系细胞中发挥作用的 HIV-1 限制因子。作为一种对策，HIV-2 的 Vpx 辅助蛋白和某些 SIV 谱系已经进化出通过诱导其泛素蛋白酶体依赖性降解来拮抗 SAMHD1。在这里，我们表明 SAMHD1 在灵长类动物进化过程中经历了强烈的正选择事件，这些事件发生在人科（长臂猿和大型猿类）和旧世界猴分支之前。鉴定出 SAMHD1 中的正选择残基，从而将 Vpx 相互作用域映射到 SAMHD1 的 C 端区域。重要的是，我们发现，虽然 SAMHD1 对 HIV-1 的限制活性在进化上得到了维持，但 Vpx 对 SAMHD1 的拮抗作用是特异性的。SAMHD1 的独特进化特征阐明了其抗病毒特异性的发展。
