How polyomaviruses penetrate the ER membrane

描述（由申请方提供）：本申请旨在阐明两种无包膜病毒多瘤病毒（Py）和SV40穿透内质网（ER）膜的分子机制。为了感染细胞，Py和SV40与宿主细胞表面称为神经节苷脂的糖脂受体结合并内化。然后病毒被运输到ER的内腔，在那里它们协同宿主细胞机器穿过ER膜并到达胞质溶胶。Py和SV40从胞质溶胶被转运到细胞核中，在那里病毒DNA的转录和复制随之发生，导致裂解感染或细胞转化。这些病毒如何穿透内质网膜到达胞质溶胶，这是一个决定性的感染事件，仍然是一个谜，这是我们打算在本提案中澄清的过程。 公共卫生相关性：鼠多瘤病毒（Py）和SV40是致肿瘤病毒。在它们的感染途径中的决定性步骤是病毒穿过称为内质网（ER）的亚细胞区室的膜的运输。然而，Py和SV 40突破ER膜的分子基础仍然是谜。在这个提议中，我们打算阐明这个神秘的过程。

DESCRIPTION (provided by applicant): This application aims to elucidate the molecular mechanism by which the two non-enveloped viruses polyomavirus (Py) and SV40 penetrate the endoplasmic reticulum (ER) membrane. To infect cells, Py and SV40 bind to glycolipid receptors called gangliosides on the host cell surface and are internalized. The viruses are then transported to the lumen of the ER where they co-opt host cell machineries to cross the ER membrane and reach the cytosol. From the cytosol, Py and SV40 are transported into the nucleus where transcription and replication of the viral DNA ensue, leading to lytic infection or cell transformation. How these viruses penetrate the ER membrane to reach the cytosol, a decisive infection event, remains mysterious and is a process we intend to clarify in this proposal. PUBLIC HEALTH RELEVANCE: The murine polyomavirus (Py) and SV40 are tumor-causing viruses. A decisive step in their infection pathway is transport of the viruses across the membrane of a sub-cellular compartment known as the endoplasmic reticulum (ER). However, the molecular basis by which Py and SV40 breach the ER membrane remains enigmatic. In this proposal, we intend to elucidate this mysterious process.