Association of hepatitis C virus replication complexes with microtubules and actin filaments is dependent on the interaction of NS3 and NS5A
Association of hepatitis C virus replication complexes with microtubules and actin filaments is dependent on the interaction of NS3 and NS5A
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DOI：
10.1128/jvi.00398-08
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Lai, Michael M. C.
中科院分区：
文献类型：
--
作者：
Lai, Chao-Kuen;Jeng, King-Song;Lai, Michael M. C.
丙型肝炎病毒 (HCV) RNA 复制复合物 (RC) 由病毒非结构 (NS) 蛋白和宿主细胞蛋白组成，可复制与细胞内膜相关的病毒 RNA 基因组。两种病毒 NS 蛋白 NS3 和 NS5A 是 RC 的重要组成部分。在这里，通过使用免疫沉淀和荧光共振能量转移测定，我们证明了 NS3 和 NS5A 与微管蛋白和肌动蛋白相互作用。此外，免疫荧光显微镜和电子显微镜显示，HCV 复制子细胞和 HCV 感染细胞中的 HCV RC 沿着微管和肌动蛋白丝排列。此外，当微管或肌动蛋白丝分别被秋水仙碱和细胞松弛素 B 解聚时，RCs 的运动受到抑制。根据我们的观察，我们提出微管和肌动蛋白丝为HCV RCs移动到细胞中的其他区域提供了轨迹，并且RCs和微管或RCs和肌动蛋白丝之间的分子相互作用是由NS3和NS5A介导的。
The hepatitis C virus (HCV) RNA replication complex (RC), which is composed of viral nonstructural (NS) proteins and host cellular proteins, replicates the viral RNA genome in association with intracellular membranes. Two viral NS proteins, NS3 and NS5A, are essential elements of the RC. Here, by using immunoprecipitation and fluorescence resonance energy transfer assays, we demonstrated that NS3 and NS5A interact with tubulin and actin. Furthermore, immunofluorescence microscopy and electron microscopy revealed that HCV RCs were aligned along microtubules and actin filaments in both HCV replicon cells and HCV-infected cells. In addition, the movement of RCs was inhibited when microtubules or actin filaments were depolymerized by colchicine and cytochalasin B, respectively. Based on our observations, we propose that microtubules and actin filaments provide the tracks for the movement of HCV RCs to other regions in the cell, and the molecular interactions between RCs and microtubules, or RCs and actin filaments, are mediated by NS3 and NS5A.