CELL BIOLOGY OF VIRUS ENTRY

描述：（改编自申请人摘要）： 在该修改的申请中提出的研究是研究细胞和 病毒过程参与的感染周期的初始阶段， 单纯疱疹病毒1型（HSV-1）和甲型流感病毒。 概述的 博士海伦纽斯，病毒粒子的使命是传递基因组， 辅助蛋白质以可复制的形式进入宿主细胞。 的 病毒颗粒必须进入胞质溶胶，从胞质溶胶中， HSV-1和流感病毒的辅助蛋白必须进入 复制的核心。 申请人建议特别侧重于 进入的HSV-1衣壳与细胞骨架元件的相互作用， 以及衣壳与核蛋白相互作用的机制 孔隙复合体 关于流感病毒，申请人建议 研究病毒核糖核蛋白（vRNP）是如何被运输进和运输出的 原子核。 将采用生物、生物化学和遗传学方法 以实现项目的总体目标。 的具体目标 建议的研究是1）分析传入HSV-1的机制 衣壳与外周细胞骨架相互作用，与动力蛋白相关， 动力蛋白和微管，以及衣壳如何移动到核孔; 2） 确定HSV-1衣壳和流感病毒vRNP如何与 核孔，以及基因组如何通过孔运输; 3） 分析新组装的流感病毒vRNP被 从细胞核输出到受感染细胞的胞质溶胶。 通过解决 这些在很大程度上被忽视的过程，申请人希望解开新的 原则和机制的一般性理解 病毒-细胞相互作用。 研究结果也可能提供新的见解 关于细胞趋向性和发病机制的更大问题。 而且 信息可能会建议新的抗病毒策略，并允许知情 病毒作为基因转移载体的应用。

DESCRIPTION: (Adapted from applicant's abstract): The overall goal of the research proposed in this revised application is to study the cellular and viral processes involved in the initial stages of the infectious cycle of herpes simplex virus type 1 (HSV-1) and influenza A virus. As outlined by Dr. Helenius, the mission of a virus particle is to deliver the genome and accessory proteins into a host cell in a replication-competent form. The virus particle must enter the cytosol, and from the cytosol the genome and accessory proteins of HSV-1 and influenza viruses have to move into the nucleus for replication. The applicant proposes to particularly focus on the interaction of incoming HSV-1 capsids with elements of the cytoskeleton, and the mechanisms by which capsids are targeted to interact with nuclear pore complexes. With regard to influenza virus, the applicant proposes to study how the viral ribonucleoproteins (vRNPs) are transported into and out of the nucleus. Biological, biochemical and genetic approaches will be used to address the overall goals of the project. The specific goals of the proposed study are 1) to analyze the mechanisms by which incoming HSV-1 capsids interact with the peripheral cytoskeleton, associate with dynein, dynactin and microtubules, and how the capsids move to the nuclear pores; 2) to determine how HSV-1 capsids and influenza virus vRNPs interact with nuclear pores, and how the genome is transported through the pore; 3) to analyze the mechanism by which newly assembled influenza virus vRNPs are exported from the nucleus to the cytosol in infected cells. By addressing these largely neglected processes, the applicant hopes to unravel new principles and mechanisms relevant for the general understanding of virus-cell interactions. The results are also likely to provide new insight on the larger questions of cell tropism and pathogenesis. Moreover, the information may suggest novel antiviral strategies, and allow informed application of viruses as vehicles for gene transfer.