Abstract：
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA virus that sits at the centre of the recent global pandemic. As a member of the coronaviridae family of viruses, it shares features such as a very large genome (>30 kb) that is replicated in a purpose-built replication organelle. Biogenesis of the replication organelle requires significant and concerted rearrangement of the endoplasmic reticulum membrane, a job that is carried out by a group of integral membrane non-structural proteins (NSP3, 4 and 6) expressed by the virus along with a host of viral replication enzymes and other factors that support transcription and replication. The primary sites for RNA replication within the replication organelle are double membrane vesicles (DMVs). The small size of DMVs requires generation of high membrane curvature, as well as stabilization of a double-membrane arrangement, but the mechanisms that underlie DMV formation remain elusive. In this review, we discuss recent breakthroughs in our understanding of the molecular basis for membrane rearrangements by coronaviruses. We incorporate established models of NSP3-4 protein-protein interactions to drive double membrane formation, and recent data highlighting the roles of lipid composition and host factor proteins (e.g. reticulons) that influence membrane curvature, to propose a revised model for DMV formation in SARS-CoV-2.
摘要：
严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）是一种正链RNA病毒，处于最近全球大流行的中心。作为冠状病毒科的一员,它具有一些特征，例如在特制的复制细胞器中复制的非常大的基因组（>30kb）。复制细胞器的生物发生需要内质网膜的显着和一致的重排，由一组完整的膜非结构蛋白（NSP3，4和6）与宿主的病毒复制酶和其他支持转录和复制的因子一起表达的工作。复制细胞器内RNA复制的主要位点是双膜囊泡(DMV)。DMV的小尺寸需要产生高的膜曲率，以及双膜布置的稳定性，但DMV形成的机制仍然难以捉摸。在这次审查中,我们讨论了我们对冠状病毒膜重排的分子基础的理解的最新突破。我们结合已建立的NSP3-4蛋白质-蛋白质相互作用模型来驱动双膜形成，和最近的数据强调了影响膜曲率的脂质成分和宿主因子蛋白（例如网状结构）的作用，提出了SARS-CoV-2中DMV形成的修正模型。
