State Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing, 100005, China.
Adv Sci (Weinh). 2023 Dec;10(36):e2305093. doi: 10.1002/advs.202305093. Epub 2023 Oct 27.
Flavivirus remodels the host endoplasmic reticulum (ER) to generate replication compartments (RCs) as the fundamental structures to accommodate viral replication. Here, a centralized replication mode of flavivirus is reported, i.e., flavivirus concentrates host ER in perinuclear main replication compartments (MRCs) for efficient replication. Superresolution live-cell imaging demonstrated that flavivirus MRCs formed via a series of events, including multisite ER clustering, growth and merging of ER clusters, directional movement, and convergence in the perinuclear region. The dynamic activities of viral RCs are driven by nonstructural (NS) proteins and are independent of microtubules and actin. Moreover, disrupting MRCs formation by small molecule compounds inhibited flavivirus replication. Overall, the findings reveal unprecedented insight into dynamic ER reorganization by flavivirus and identify a new inhibition strategy.
黄病毒重塑宿主内质网 (ER) 以产生复制区 (RCs)，作为容纳病毒复制的基本结构。本文报道了黄病毒的一种集中式复制模式，即黄病毒将宿主 ER 集中在核周主要复制区 (MRC) 中以进行有效的复制。超分辨率活细胞成像显示，黄病毒 MRC 是通过一系列事件形成的，包括 ER 簇的多部位聚集、ER 簇的生长和融合、定向运动以及在核周区域的汇聚。病毒 RC 的动态活动由非结构 (NS) 蛋白驱动，与微管和肌动蛋白无关。此外，小分子化合物破坏 MRC 的形成可抑制黄病毒的复制。总的来说，这些发现揭示了黄病毒对 ER 动态重组的前所未有的见解，并确定了一种新的抑制策略。
