PATHOBIOLOGY OF PARAMYXOVIRUS--VIRUS ASSEMBLY

副粘病毒，一组包膜的非分段负链RNA

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.