Laboratory of Systems Virology, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan.
Graduate School of Medicine, Kyoto University, Kyoto, Japan.
PLoS Pathog. 2020 Sep 10;16(9):e1008812. doi: 10.1371/journal.ppat.1008812. eCollection 2020 Sep.
The APOBEC3 deaminases are potent inhibitors of virus replication and barriers to cross-species transmission. For simian immunodeficiency virus (SIV) to transmit to a new primate host, as happened multiple times to seed the ongoing HIV-1 epidemic, the viral infectivity factor (Vif) must be capable of neutralizing the APOBEC3 enzymes of the new host. Although much is known about current interactions of HIV-1 Vif and human APOBEC3s, the evolutionary changes in SIV Vif required for transmission from chimpanzees to gorillas and ultimately to humans are poorly understood. Here, we demonstrate that gorilla APOBEC3G is a factor with the potential to hamper SIV transmission from chimpanzees to gorillas. Gain-of-function experiments using SIVcpzPtt Vif revealed that this barrier could be overcome by a single Vif acidic amino acid substitution (M16E). Moreover, degradation of gorilla APOBEC3F is induced by Vif through a mechanism that is distinct from that of human APOBEC3F. Thus, our findings identify virus adaptations in gorillas that preceded and may have facilitated transmission to humans.
APOBEC3 脱氨酶是强大的病毒复制抑制剂和跨物种传播的障碍。为了使猿猴免疫缺陷病毒（SIV）能够传播到新的灵长类宿主，就像多次发生的那样，为正在进行的 HIV-1 流行奠定了基础，病毒感染力因子（Vif）必须能够中和新宿主的 APOBEC3 酶。尽管人们对 HIV-1 Vif 和人类 APOBEC3 的当前相互作用有了很多了解，但对于从黑猩猩传播到大猩猩，最终传播到人类所需的 SIV Vif 的进化变化却知之甚少。在这里，我们证明了大猩猩 APOBEC3G 是一种具有潜在能力的因子，可以阻碍 SIV 从黑猩猩传播到大猩猩。使用 SIVcpzPtt Vif 的功能获得实验表明，这种障碍可以通过单个 Vif 酸性氨基酸取代（M16E）来克服。此外，Vif 通过一种与人类 APOBEC3F 不同的机制诱导大猩猩 APOBEC3F 的降解。因此，我们的发现确定了大猩猩中病毒的适应性，这些适应性先于并可能促进了向人类的传播。
