How polyomaviruses penetrate the ER membrane

摘要 该应用程序的目标是探索无包膜多瘤病毒（PyV）如何劫持一个 新的内质网（ER）膜蛋白复合物称为EMC， 促进其ER向胞质膜渗透，这是决定性的感染步骤。造成 感染后，PyV经历受体介导的内吞作用，从血浆中运输 膜到ER，在那里它随后穿透ER膜到达ER膜。 胞质液病毒从胞质溶胶移动到细胞核，在细胞核中转录和 病毒基因组的复制随之发生，导致裂解性感染或细胞转化。 虽然我的实验室和其他人已经提供了重要的见解ER管腔和 细胞溶质事件驱动PyV ER到细胞溶质膜转运，仍然是一个 我们理解的主要差距是ER脂质双层中的事件， 和胞质反应。因此，本提案的目的是澄清ER如何 膜蛋白复合物EMC通过以下方式促进PyV ER膜渗透： 在ER腔和胞质溶胶中的潜在偶联反应。

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.