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。 要研究的病毒系统是 Semliki森林病毒（SFV）和甲型流感病毒， 证明相关的模型系统的一般问题的早期 病毒-细胞相互作用。 总体目标是定义分子 和细胞术语的以下步骤进入：内化 病毒颗粒通过内吞作用， 膜融合，基因组的脱壳，以及运输到 复制和转录的细胞质或细胞核定位。 我们希望对这些原则有更深入的了解 潜在的病毒致病性和细胞嗜性以及基本的 生物现象如膜融合、核靶向 以及细胞间的相互作用。 具体方面包括更详细的定义， 内吞细胞器中，酸触发的病毒融合 会发生 病毒融合过程中的构象变化 蛋白质酸诱导的活性将详细表征， 强调SFV的固醇依赖性（现在被认为是一种 病毒之间的共同属性）和病毒之间的相互作用。 融合因子和融合膜。 的机理 三聚体血凝素的作用， 流感病毒，将使用杂交分子进行研究， 由不同亚单位组成的三聚体。 的命运 渗透后的核衣壳将遵循生化 和免疫化学方法。 此外，我们将努力解决 诱导基因组脱壳的信号，并分析基因组中的 脱膜的分子机制， 将基因组转运至SFV特异性致细胞病变的空泡， 和流感到细胞核，将进行研究。 各种 从冰冻切片的免疫细胞化学， 将使用反义寡核苷酸的批量递送。

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.