Molecular and Cellular Biology Graduate Program, University of Washington, Seattle, WA 98195, USA.
Cell Host Microbe. 2012 Jan 19;11(1):91-8. doi: 10.1016/j.chom.2011.11.010.
APOBEC3G (A3G) is a host cytidine deaminase that inhibits retroviruses. HIV and related primate lentiviruses encode Vif, which counteracts A3G by inducing its degradation. This Vif-mediated A3G inhibition is species specific, suggesting that the A3G-Vif interaction has evolved as primate lentiviruses have adapted to their hosts. We examined the evolutionary dynamics of the A3G-Vif interaction within four African green monkey (AGM) subspecies, which are each naturally infected with a distinct simian immunodeficiency virus (SIV). We identified single amino acid changes within A3G in two AGM subspecies that render it resistant to Vif proteins, except for Vif from the viruses that naturally infect these subspecies. Moreover, experimental infection of AGMs shows that Vif can rapidly adapt to these arising Vif-resistant A3G genotypes. These data suggest that despite being generally nonpathogenic in its natural host, SIV infection selects for Vif-resistant forms of A3G in AGM populations, driving Vif counterevolution and functional divergence.
APOBEC3G (A3G) 是一种宿主胞嘧啶脱氨酶，可抑制逆转录病毒。HIV 和相关的灵长类慢病毒编码 Vif，它通过诱导 A3G 的降解来拮抗 A3G。这种 Vif 介导的 A3G 抑制是种属特异性的，表明 A3G-Vif 相互作用是随着灵长类慢病毒适应其宿主而进化的。我们在四个非洲绿猴（AGM）亚种中研究了 A3G-Vif 相互作用的进化动态，这四个亚种都自然感染了不同的猿猴免疫缺陷病毒（SIV）。我们在两个 AGM 亚种中发现了 A3G 内的单个氨基酸变化，使其对除了自然感染这些亚种的病毒的 Vif 蛋白具有抗性。此外，AGM 的实验感染表明，Vif 可以快速适应这些新出现的对 Vif 有抗性的 A3G 基因型。这些数据表明，尽管 SIV 在其自然宿主中通常没有致病性，但 SIV 感染在 AGM 群体中选择了对 Vif 有抗性的 A3G 形式，推动了 Vif 的反向进化和功能分化。
