PATHOBIOLOGY OF PARAMYXOVIRUS--VIRUS ASSEMBLY

副粘病毒是一类有包膜的非分节段负链RNA 病毒，包括许多重要的动物和人类病原体， 呼吸道合胞病毒（RSV）、副流感病毒、腮腺炎病毒和 麻疹病毒本项目的长期目标是阐明 感染性病毒颗粒的组装和出芽步骤。 在这个项目中，我们将使用仙台病毒，一种小鼠病原体， 作为副粘病毒模型被广泛研究。我们最近的研究表明 仙台病毒基质（M）蛋白，病毒中的关键成分， 形态发生，与仙台病毒糖蛋白（F和HN）相互作用。我们 最近也表明仙台病毒F和HN而不是M与 Triton-X 100不溶性宿主脂质在通过胞吐转运期间 通路 本项目的具体目标是：a）确定 参与病毒蛋白F、HN和M极化转运的机制 组装位点，B）阐明M蛋白如何与F、HN 蛋白质和核衣壳结构，c）决定M的性质 帮助病毒组装和出芽的蛋白质，d）探索 组装过程中的细胞成分如细胞骨架。这些 研究将在仙台病毒感染的细胞以及 从克隆的cDNA表达病毒蛋白的细胞。 拟议的研究将阐明，在分子水平上，步骤 参与病毒的装配和形态发生，帮助我们设计 干扰这些步骤的抗病毒策略。这样的方法可能 由于目前没有疫苗或抗病毒治疗， 对于重要的儿童疾病，如RSV，由成员引起的副流感， 副粘病毒组。

Paramyxoviruses, a group of enveloped nonsegmented negative strand RNA viruses, include a number of important animal and human pathogens such as respiratory syncytial virus (RSV), parainfluenza viruses, mumps virus and measles virus. The long term goal of this project is to elucidate the steps involved in the assembly and budding of infectious virus particles. In this project, we will use Sendai virus, a mouse pathogen, which has been extensively studied as a model paramyxovirus. We have recently shown that Sendai viral matrix (M) protein, a key component in viral morphogenesis, interacts with Sendai viral glycoproteins (F and HN). We have also recently shown that Sendai virus F and HN but not M bind to Triton-X 100 insoluble host lipids during transport through the exocytic pathway. The specific objectives of this project will be to a) define the mechanism involved in polarized transport of viral proteins F, HN and M to the site of assembly, b) elucidate how M protein interacts with F, HN proteins and the nucleocapsid structure, c) determine the properties of M protein which aid in viral assembly and budding, d) to explore the role of cellular components like cytoskeleton in the assembly process. These studies will be carried out in Sendai virus-infected cells as well as in cells expressing viral proteins from cloned cDNAs. The proposed studies will elucidate, at molecular level, the steps involved in viral assembly and morphogenesis and help us to design antiviral strategy for interfering with these steps. Such approaches may be important since no vaccine or antiviral therapy is currently available for important childhood diseases like RSV, paraflu caused by the members of paramyxovirus group.