Ai Youwei, Ma Jianzhang, Wang Xiaojun
Present address: National Institute of Biological Sciences, Beijing, PR China.
College of Wildlife Resources, Northeast Forestry University, Hexing Road, Harbin 150040, PR China.
J Gen Virol. 2017 May;98(5):1113-1121. doi: 10.1099/jgv.0.000749. Epub 2017 May 18.
Lentiviruses threaten human and animal health. Virion infectivity factor (Vif) is essential for the infectivity of most lentiviruses, except for the equine infectious anaemia virus (EIAV). Vif promotes viral infectivity by recruiting a Cullin-based E3 ligase to induce the degradation of a class of host restriction factors, named APOBEC3. Core binding factor beta (CBF-β) is necessary for several primate lentiviral Vif functions, including HIV-1 Vif. Although much progress has been made in understanding the contribution of CBF-β to Vif function, the precise mechanism has not yet been fully elucidated. In this study, we found that an interaction with CBF-β altered the oligomerization and subcellular distribution pattern and increased the stability of two primate lentiviral Vifs, HIV-1 Vif and Macaca simian immunodeficiency virus (SIVmac) Vif. Moreover, using a CBF-β loss-of-function mutant, we demonstrated that the interaction between CBF-β and Vif was not sufficient for Vif assistance; a region including F68 in CBF-β was also required for the stability and function of Vif. For the first time, this study separates the binding and regulating processes of CBF-β when it is promoting Vif function, which further extends our understanding of the biochemical regulation of Vif by CBF-β.
慢病毒威胁着人类和动物的健康。病毒体感染性因子（Vif）对于大多数慢病毒的感染性至关重要，但马传染性贫血病毒（EIAV）除外。Vif通过招募一种基于Cullin的E3连接酶来诱导一类名为载脂蛋白B编辑酶催化多肽样3（APOBEC3）的宿主限制因子的降解，从而促进病毒感染性。核心结合因子β（CBF-β）对于几种灵长类慢病毒Vif的功能是必需的，包括HIV-1 Vif。尽管在理解CBF-β对Vif功能的贡献方面已经取得了很大进展，但其精确机制尚未完全阐明。在本研究中，我们发现与CBF-β的相互作用改变了两种灵长类慢病毒Vif（HIV-1 Vif和猕猴猿猴免疫缺陷病毒（SIVmac）Vif）的寡聚化和亚细胞分布模式，并增加了它们的稳定性。此外，使用CBF-β功能缺失突变体，我们证明CBF-β与Vif之间的相互作用不足以提供Vif辅助；CBF-β中包括F68的区域对于Vif的稳定性和功能也是必需的。本研究首次分离了CBF-β在促进Vif功能时的结合和调节过程，这进一步扩展了我们对CBF-β对Vif生化调节的理解。
