Rotavirus Viroplasm Biogenesis Involves Microtubule-Based Dynein Transport Mediated by an Interaction between NSP2 and Dynein Intermediate Chain

文献类型： 外文期刊

第一作者： Jing, Zhaoyang

作者： Jing, Zhaoyang;Shi, Hongyan;Chen, Jianfei;Shi, Da;Liu, Jianbo;Guo, Longjun;Tian, Jin;Wu, Yang;Dong, Hui;Ji, Zhaoyang;Zhang, Jiyu;Zhang, Liaoyuan;Zhang, Xin;Feng, Li

作者机构：

关键词： dynein intermediate chain (DIC); dynein transport; fusion; formation; microtubule based; NSP2; rotavirus; viroplasm

期刊名称：JOURNAL OF VIROLOGY （ 影响因子：5.103； 五年影响因子：5.078 ）

ISSN： 0022-538X

年卷期： 2021 年 95 卷 21 期

页码：

收录情况： SCI

摘要： Rotaviruses are the causative agents of severe and dehydrating gastro-enteritis in children, piglets, and many other young animals. They replicate their genomes and assemble double-layered particles in cytoplasmic electron-dense inclu-sion bodies called "viroplasms." The formation of viroplasms is reportedly associated with the stability of microtubules. Although material transport is an important func-tion of microtubules, whether and how microtubule-based transport influences the formation of viroplasms are still unclear. Here, we demonstrate that small viroplasms move and fuse in living cells. We show that microtubule-based dynein transport affects rotavirus infection, viroplasm formation, and the assembly of transient envel-oped particles (TEPs) and triple-layered particles (TLPs). The dynein intermediate chain (DIC) is shown to localize in the viroplasm and to interact directly with non-structural protein 2 (NSP2), indicating that the DIC is responsible for connecting the viroplasm to dynein. The WD40 repeat domain of the DIC regulates the interaction between the DIC and NSP2, and the knockdown of the DIC inhibited rotaviral infec-tion, viroplasm formation, and the assembly of TEPs and TLPs. Our findings show that rotavirus viroplasms hijack dynein transport for fusion events, required for maxi-mal assembly of infectious viral progeny. This study provides novel insights into the intracellular transport of viroplasms, which is involved in their biogenesis. IMPORTANCE Because the viroplasm is the viral factory for rotavirus replication, viro-plasm formation undoubtedly determines the effective production of progeny rotavirus. Therefore, an understanding of the virus-host interactions involved in the biogenesis of the viroplasm is critical for the future development of prophylactic and therapeutic strat-egies. Previous studies have reported that the formation of viroplasms is associated with the stability of microtubules, whereas little is known about its specific mechanism. Here, we demonstrate that rotavirus viroplasm formation takes advantage of microtubule-based dynein transport mediated by an interaction between NSP2 and the DIC. These findings provide new insight into the intracellular transport of viroplasms.

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