PATHOBIOLOGY OF PARAMYXOVIRUS--VIRUS ASSEMBLY

副粘病毒，一组包膜的非节段性负链RNA 病毒，包括一些重要的动物和人类病原体，如 呼吸道合胞病毒(RSV)、副流感病毒、腮腺炎病毒和 麻疹病毒。这个项目的长期目标是阐明 与传染性病毒颗粒的组装和萌发有关的步骤。 在这个项目中，我们将使用仙台病毒，一种老鼠的病原体，它已经 作为一种模式副粘病毒被广泛研究。我们最近展示了 仙台病毒基质(M)蛋白，病毒的关键成分 形态发生，与仙台病毒糖蛋白(F和HN)相互作用。我们 最近还表明，仙台病毒F和HN但不与M结合 Triton-X 100不溶性宿主脂在通过胞外转运过程中 路径。本项目的具体目标将是a)定义 病毒蛋白F、HN和M的极化转运机制 B)阐明M蛋白如何与F、HN相互作用 蛋白质和核衣壳结构，c)决定M的性质 有助于病毒组装和发芽的蛋白质，d)探索 组装过程中的细胞组件，如细胞骨架。这些 研究将在仙台病毒感染的细胞以及在 从克隆的cDNA中表达病毒蛋白的细胞。 拟议的研究将在分子水平上阐明这些步骤 参与病毒的组装和形态形成，并帮助我们设计 干扰这些步骤的抗病毒策略。这种方法可能 很重要，因为目前还没有疫苗或抗病毒疗法 对于重要的儿童疾病，如RSV，Paraflu由成员引起 属于副粘病毒组。

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.