CELL BIOLOGY OF VIRUS ENTRY

我们正在研究病毒进入宿主的机制 细胞并启动复制。拟研究的病毒系统包括 塞姆利基森林病毒(SFV)和甲型流感病毒，它们已经 对于早期的一般问题，证明了相关的模型系统 病毒与细胞的相互作用。总体目标是在分子上定义 和元胞术语进入的以下步骤：内部化 病毒颗粒通过内吞作用，从内吞体内穿透 膜融合，揭开基因组的外衣，并将其输送到 复制和转录的细胞质或核位置。 我们希望对这些原则有更深的理解。 潜在的病毒致病性和细胞嗜性以及基本的 膜融合、核靶向等生物现象 以及细胞隔间之间的相互作用。 具体方面包括更详细的定义 酸引发病毒融合的内吞细胞器 发生了。病毒融合过程中的构象变化 在酸诱导的蛋白质中，活性将用 强调SFV的类固醇依赖(现在被认为是一种 病毒之间的共同属性)以及病毒之间的相互作用 融合因子和融合膜。它的作用机制 三聚体血凝素的作用，融合因子 流感病毒，将使用由以下组成的杂交分子进行研究 由不同亚基组成的三聚体。美国人的命运 穿透后的核衣壳将进行生化反应 和免疫化学方法。此外，我们将努力解决 诱导基因组被揭开的信号并分析 脱涂层发生的分子机制，即 将基因组运输到SFV特异的细胞病变空泡， 和流感到核，将被调查。各种各样的 方法从冰冻切片的免疫细胞化学到 将使用批量运送反义寡核苷酸。

We are studying the mechanism whereby viruses enter their host cells and initiate replication. The virus systems to be studied are Semliki Forest virus (SFV) and Influenza A virus, which have proven relevant model systems for the general problems of early virus-cell interactions. The overall aim is to define on molecular and cellular terms the following steps in entry: internalization of the virus particles by endocytosis, penetration from endosomes by membrane fusion, uncoating of the genome, and transport to the cytoplasmic or nuclear location of replication and transcription. We hope to obtain a deeper understanding of the principles underlying viral pathogenicity and cell tropism as well as of basic biological phenomena such as membrane fusion, nuclear targeting and the interaction between cellular compartments. The specific aspects include a more detailed definition of endocytic organelles where acid-triggered fusion of the viruses takes place. The conformational changes in the viral fusion proteins acid-induced, activity will be characterized in detail with emphasis on the sterol dependence of SFV (now recognized as a common property among viruses) and the interaction between the fusion factors and the fusing membranes. The mechanism of action of the trimeric hemagglutinin, the fusion factor of Influenza virus, will be studied using hybrid molecules made up of trimers consisting of different subunits. The fate of the nucleocapsids after penetration will be followed by biochemical and immunochemical methods. We will, moreover, try to resolve the signals which induce uncoating of the genome and analyze the molecular mechanism by which uncoating takes place, the transport of the genome to the SFV-specific cytopathic vacuols, and Influenza to the nucleus, will be investigated. A variety of methods ranging from immunocytochemistry on frozen sections to bulk delivery of anti-sense oligonucleotides will be used.