Vif-CBFβ interaction is essential for Vif-induced cell cycle arrest
Vif-CBFβ interaction is essential for Vif-induced cell cycle arrest
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Vif-CBF beta 相互作用对于 Vif 诱导的细胞周期停滞至关重要
DOI：
10.1016/j.bbrc.2019.02.136
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发表时间：
2019-04-16
影响因子：
3.1
通讯作者：
Yu, Xiao-Fang
中科院分区：
文献类型：
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作者：
Du, Juan;Rui, Yajuan;Yu, Xiao-Fang
HIV-1 Vif和宿主因子CBF β之间的相互作用导致Vif-Cul 5-EloB/C泛素连接酶（E3复合物）的组装。通过诱导E3复合物的形成，Vif耗尽宿主APOBEC 3限制因子并促进HIV-1感染。此外，已知Vif将宿主细胞阻滞在G2/M期（G2阻滞），有利于HIV-1复制并有助于CD 4（+）T细胞的耗竭。然而，CBF β是否也参与Vif诱导的细胞周期阻滞仍不清楚。在本研究中，我们报告说，CBF β是一个重要的因素，VIF诱导的G2期阻滞。降低内源性CBF β表达显著损害Vifs在细胞周期调节中的效力。此外，用CBF β和Vif突变体进行的测试表明，Vif-CBF β相互作用对于Vif诱导G2停滞至关重要。此外，抑制因子对Vif-hijacked E3复合物或蛋白酶体介导的蛋白水解也取消了Vifs的能力，导致G2期阻滞。总的来说，我们的数据表明，Vif通过耗尽一种未知的细胞因子诱导G2期阻滞，其中CBF β的参与至关重要。另一方面，我们的数据还表明，靶向Vif-CBF β相互作用的抗病毒药物有可能消除Vifs导致宿主细胞中APOBEC 3降解以及G2阻滞的能力，从而减少HIV-1复制和Vif-induced CD 4（+）T细胞耗竭。(C)2019爱思唯尔公司All rights reserved.
Interaction between HIV-1 Vif and host factor CBF beta leads to the assembly of the Vif-Cul5-EloB/C ubiquitin ligase (E3 complex). By inducing the formation of E3 complex, Vif depletes host APOBEC3 restriction factors and promotes HIV-1 infection. In addition, Vif is known to arrest host cells at G2/M phase (G2 arrest), benefiting HIV-1 replication and contributing to the depletion of CD4(+) T cells. However, whether CBF beta is also involved in Vif-induced cell cycle arrest remains unclear. In the present study, we report that CBF beta is an essential factor for Vif-induced G2 arrest. Reducing endogenous CBF beta expression significantly compromised Vifs potency in cell cycle regulation. In addition, tests with CBF beta and Vif mutants indicated that Vif-CBF beta interaction is crucial for Vif to induce G2 arrest. Furthermore, suppressors against Vif-hijacked E3 complex or proteasome-mediated proteolysis also abolished Vifs ability to cause G2 arrest. In general, our data indicated that Vif induces G2 arrest through depletion of a yet-unknown cellular factor, where the involvement of CBF beta is essential. On the other hand, our data also suggested that, antiviral drugs targeting the Vif-CBF beta interaction have the potential to abolish Vifs ability to cause APOBEC3 degradation as well as G2 arrest in host cells, thus reducing both HIV-1 replication and Vif-induced CD4(+) T-cell depletion. (C) 2019 Elsevier Inc. All rights reserved.