Arthropod vectored viruses are a major cause of human disease. The alphaviruses are a group of arthropod vectored agents which are responsible for a variety of severe forms of encephalitis in man and domestic animals. The mosquito Aedes albopictus is a major carrier of viruses including the alphaviruses. The appearance and wide spread dissemination of this mosquito in north America has raised legitimate concerns regarding the potential hazards these viruses represent in the United States. Aedes albopictus collected in North America have been shown to be effective vectors of a number of alphaviruses capable of producing severe human infections. Sindbis virus is the prototype of the alphavirus group and it has been shown that Aedes albopictus is an efficient vector of Sindbis virus supporting the contention that Sindbis is a good model for the virus system. The research described in this application focuses ont he biology of Sindbis virus the alphavirus prototype. This research will investigate the organization of the proteins in the mature virion and will examine the process of assembly of the virus from its component parts. This research program has three distinct long term goals. These goals are to: 1): Determine the organization of the structural components of Sindbis virus. 2): determine the protein-protein interactions which are critical for the three dimensional structure of the virus particle and describe the process by which these proteins fold and associate to produce this structure. 3): determine the mechanism by which this three dimensional protein aggregate is disassembled as the virus infects a cell. In global terms this research examines the structure, assembly and function of this model membrane containing virus. The research to be conducted has broader implications for understanding the process by which complex protein oligomers are folded and assembled into functional entities in eucaryotic cells. Information on the process of assembly and disassembly of sindbis virus may suggest new targets for development of drugs which interrupt the replication cycle of membrane containing viruses. In addition, the identification of virus mutants which assembly correctly but do not disassemble may provide a new approach to vaccine development.
