How infectious SARS-CoV-2 exploits two ER membrane proteins to promote infection

摘要 SARS-CoV-2利用内质网(ER)功能促进其 感染生命周期。尽管它强烈依赖内质网，但它所依赖的分子基础 SARS-CoV-2劫持ER因子以促进这个生命周期的既定步骤 不清楚。利用传染性SARS-CoV-2，我们最近鉴定了两个ER膜 蛋白质-RTN3和SigmaR1-作为支持病毒感染的关键宿主因素。我们的 研究结果进一步表明，RTN3在病毒复制中发挥作用，而SigmaR1在病毒复制中发挥作用 在病毒分泌中起作用。然而，SARS-CoV-2如何利用RTN3的活性 和SigmaR1来完成这两个不同的任务，从机械的角度来说，是完全 未知。因此，这种应用的目的是阐明分子基础 通过这两种ER膜因子促进SARS的复制和分泌- CoV-2。我们相信，这些见解不仅将阐明基本的感染机制 SARS-CoV-2的流行，但鉴于持续的全球新冠肺炎大流行，可能导致 开发有效的抗病毒药物，以减轻SARS-CoV-2的破坏性影响。

Abstract SARS-CoV-2 exploits the function of the endoplasmic reticulum (ER) to promote its infection life cycle. Despite its strong reliance on the ER, the molecular basis by which SARS-CoV-2 hijacks ER factors to promote defined steps of this life cycle remains unclear. Using infectious SARS-CoV-2, we recently identified two ER membrane proteins – RTN3 and SigmaR1 – as critical host factors that support virus infection. Our findings further reveal that RTN3 plays a role in viral replication, while SigmaR1 exerts a function in viral secretion. However, how SARS-CoV-2 exploits the activities of RTN3 and SigmaR1 to accomplish these two distinct tasks, in mechanistic terms, is completely unknown. Accordingly, the objective of this application is to elucidate the molecular basis by which these two ER membrane factors promote replication and secretion of SARS- CoV-2. We believe these insights will not only illuminate the basic infection mechanism of SARS-CoV-2, but given the continuing global COVID-19 pandemic, may lead to the development of effective anti-virals to blunt the devastating impact of SARS-CoV-2.