Dual role of the amphipathic helix of hepatitis C virus NS5A in the viral polyprotein cleavage and replicase assembly
Dual role of the amphipathic helix of hepatitis C virus NS5A in the viral polyprotein cleavage and replicase assembly
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丙型肝炎病毒 NS5A 两亲螺旋在病毒多蛋白裂解和复制酶组装中的双重作用
DOI：
10.1016/j.virol.2019.07.017
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发表时间：
2019
期刊：
影响因子：
3.7
通讯作者：
Yi Zhigang
中科院分区：
文献类型：
--
作者：
Zhang Yang;Zhao Xiaomin;Zou Jingyi;Yuan Zhenghong;Yi Zhigang
在宿主细胞内膜上组装病毒复制酶是几乎所有正链RNA病毒的病毒复制的常见策略。了解复制酶的关键模块如何参与复制酶组装可以提供对复制酶组装途径的见解。在此，我们以HCV为模型，剖析了NS 5A的两亲性螺旋（AH）在病毒复制酶组装中的作用。结果表明，NS 5A的膜锚定能力较好。相反，AH在病毒复制酶组装中起着双重作用：正确定位复制酶模块以进行有效的多蛋白加工，并参与复制酶内的蛋白质-蛋白质相互作用。AH的这种性质可能作为一个有吸引力的直接抗病毒靶点。
Assembling a viral replicase on host intracellular membranes is a common strategy for viral replication of almost all of the positive-strand RNA viruses. Understanding how the key modules of the replicase are involved in the replicase assembly may provide insights into the pathway of the replicase assembly. Herein, by using HCV as a model, we dissect the roles of the amphipathic helix (AH) of NS5A, a key repilcase component, in the viral replicase assembly. The results show that the AH is dispensable for membrane anchoring of NS5A. Instead, AH plays a dual role in the viral replicase assembly: positions a replicase module properly for efficient polyprotein processing and participates in protein-protein interactions within the replicase. This property of AH may serve as an attractive direct anti-viral target.