Moloney leukemia virus 10 (MOV10) inhibits the degradation of APOBEC3G through interference with the Vif-mediated ubiquitin-proteasome pathway.
Moloney leukemia virus 10 (MOV10) inhibits the degradation of APOBEC3G through interference with the Vif-mediated ubiquitin-proteasome pathway.
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莫洛尼白血病病毒 10 (MOV10) 通过干扰 Vif 介导的泛素蛋白酶体途径抑制 APOBEC3G 的降解
DOI：
10.1186/s12977-017-0382-1
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发表时间：
2017-12-19
期刊：
影响因子：
3.3
通讯作者：
Zhang H
中科院分区：
文献类型：
--
作者：
Chen C;Ma X;Hu Q;Li X;Huang F;Zhang J;Pan T;Xia J;Liu C;Zhang H
MOV 10蛋白具有ATP依赖的5′-3′ RNA解旋酶活性，属于UPF 1 p超家族。它可以在多个阶段抑制人类免疫缺陷病毒1型（HIV-1）的复制，并与载脂蛋白-B-mRNA编辑酶催化多肽样3G（APOBEC 3G或A3 G）相互作用，APOBEC 3G是胞苷脱氨酶家族的一员，对HIV-1感染具有强效抑制作用。然而，HIV-1编码的病毒体感染因子（Vif）蛋白通过泛素-蛋白酶体系统（UPS）特异性介导A3 G的降解。我们证明，MOV 10通过抑制Vif-CBF-β-Cullin 5-ElonginB-ElonginC复合物的组装来抵消Vif介导的A3 G降解。通过干扰UPS，MOV 10增强HIV-1感染细胞和病毒体中A3 G的水平，并协同抑制HIV-1的复制和感染性。此外，MOV 10的DEAG盒是抑制Vif介导的A3 G降解所必需的，因为DEAG盒突变体显著丧失了这种能力。我们的研究结果证明了MOV 10的抗HIV-1功能中涉及的一种新机制。鉴于MOV 10和A3 G都属于干扰素抗病毒系统，它们对HIV-1的协同抑制表明这些蛋白质可能在抗病毒功能中发挥复杂的作用。
MOV10 protein has ATP-dependent 5′–3′ RNA helicase activity and belongs to the UPF1p superfamily. It can inhibit human immunodeficiency virus type 1 (HIV-1) replication at multiple stages and interact with apolipoprotein-B-mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G or A3G), a member of the cytidine deaminase family that exerts potent inhibitory effects against HIV-1 infection. However, HIV-1-encoded virion infectivity factor (Vif) protein specifically mediates the degradation of A3G via the ubiquitin–proteasome system (UPS). We demonstrate that MOV10 counteracts Vif-mediated degradation of A3G by inhibiting the assembly of the Vif-CBF-β-Cullin 5-ElonginB-ElonginC complex. Through interference with UPS, MOV10 enhances the level of A3G in HIV-1-infected cells and virions, and synergistically inhibits the replication and infectivity of HIV-1. In addition, the DEAG-box of MOV10 is required for inhibition of Vif-mediated A3G degradation as the DEAG-box mutant significantly loses this ability. Our results demonstrate a novel mechanism involved in the anti-HIV-1 function of MOV10. Given that both MOV10 and A3G belong to the interferon antiviral system, their synergistic inhibition of HIV-1 suggests that these proteins may play complicated roles in antiviral functions.
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影响因子：
3.7
作者：
Huang, Feng;Zhang, Junsong;Zhang, Hui
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通讯作者：
Krogan, Nevan J.
影响因子：
3.3
作者：
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影响因子：
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作者：
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通讯作者：
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