How polyomaviruses penetrate the ER membrane

摘要 这个应用程序的目标是探测非包膜多瘤病毒(PYV)是如何劫持 一种名为EMC TO的新型内质网膜蛋白复合体 促进其内质网向细胞膜的渗透，是感染的决定性一步。引起 感染后，PYV经历受体介导的内吞作用，从血浆转运 膜到内质网，在那里它随后穿透内质网膜到达 胞浆。从胞浆中，病毒进入细胞核，在那里转录和 随后病毒基因组复制，导致裂解感染或细胞转化。 虽然我的实验室和其他人提供了对ER Lumina和 驱动PYV ER到胞浆膜运输的胞液事件，什么仍然是 我们理解中的主要差距是内质网脂双层中连接管腔的事件 和胞浆反应。因此，这项提案的目的是澄清ER如何 膜蛋白复合体EMC通过以下途径促进PYV ER膜穿透 内质网管腔和胞浆中的潜在偶联反应。

Abstract This application's goal is to probe how the non-enveloped polyomavirus (PyV) hijacks a novel endoplasmic reticulum (ER) membrane protein complex called the EMC to promote its ER-to-cytosol membrane penetration, a decisive infection step. To cause infection, PyV undergoes receptor-mediated endocytosis, trafficking from the plasma membrane to the ER where it subsequently penetrates the ER membrane to reach the cytosol. From the cytosol, the virus mobilizes into the nucleus where transcription and replication of the viral genome ensue, leading to lytic infection or cellular transformation. While my laboratory and others have provided significant insights into ER luminal and cytosolic events that drive PyV ER-to-cytosol membrane transport, what remains a major gap in our understanding are events in the ER lipid bilayer that link the luminal and cytosolic reactions. Accordingly, this proposal's objective is to clarify how the ER membrane protein complex EMC facilitates PyV ER membrane penetration by potentially coupling reactions in the ER lumen and in the cytosol.