Functional Roles of Host Factors in Plus-Stranded RNA Viruses Replication

The long-term objective of this project is to understand the virus-host interactions that govern whether a host is susceptible or resistant to a virus. For positive-strand RNA viruses, these interactions affect virus entry, genome expression, genome replication, assembly, intercellular movement, and pathogenicity. Many of the intracellular virus-host interactions involving these viruses are highly conserved between animals, plants and eukaryotic microbes. In addition, virus-host interactions can have profound effects on host development. To identify functionally important host compatibility or defense factors, the PI will use Japanese Encephalitis virus (JEV) and Dengue virus (DENV), Enterovirus as well as the hepatitis C virus, the type species of flaviviruses genus to elucidate the molecular and mechanistic roles of host factors involved in the RNA replication. The project has three major specific aims: 1) Identification of numerous host factors affecting/involving viral replication by using a systems biology approach, including genome-wide screens and proteomics approaches. 2) Dissecting the roles of three RNA-binding host proteins in the plus-stranded RNA viruses replicaton: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the p68 DEAD-box RNA helicase homolog Dpb2 and translation elongation factor EF-1alpha, all of which bind to plant plus-stranded RNA viruses and also known to interact with Hepatitis C virus, West Nile virus, dengue 4 virus and hepatitis A virus RNAs, suggesting that host factors might play similar roles in replication of these viruses. 3) Roles of Vacuolar Protein sorting proteins in RNA virus replication. The following are the major strengths of the proposal: (i) Viral RNA replication is clearly of immense importance for viruses to infect all types of living organisms. (ii) It has been reported that the utilization of yeast as a model host has promoted rapid and significant progress in the understanding of the roles of host factors in viral replication. The PI has had well hands-on experienced and knowledge of using yeast for studying the mechanism of host factors involvement in viral RNA replication. (iii) This research is expected to lead to groundbreaking new discoveries in viral RNA replication.

Project ID:PC9808-0955
External Project ID:NSC98-2320-B182-036-MY2