Positive-strand RNA viruses are the largest among 7 viral classes, including many important human and animal pathogens as well as the great majority of plant viruses. Some examples include Zika virus, hepatitis C virus, foot and mouth disease virus, and cucumber mosaic virus. Despite infecting very different hosts and causing distinct symptoms, viruses in this class use similar strategies to replicate their genomic RNAs. As an indispensable process, viral replication also represents an excellent target for the development of antiviral strategies that should provide strong protection and apply to a wide range of important viral pathogens. This project aims to characterize the contributions of viral replication proteins and certain host proteins to viral replication and is expected to provide new insights on mechanisms required for viral replication as well as novel approaches for virus control. The project is also expected to provide undergraduate students from underrepresented groups with valuable experience in translational plant science and inspire them to seek more research opportunities and attend graduate schools in the field of plant science.
A highly conserved feature of positive-strand RNA virus replication is that these viruses remodel host intracellular membranes to form their viral replication complexes (VRCs), an essential step in viral replication. Despite its critical importance, the mechanisms by which membranes are remodeled, the lipid microenvironment within VRCs, and the host proteins required for such processes are poorly understood. This project aims to address aforementioned knowledge gaps by using brome mosaic virus (BMV), a model virus used to study the common features shared by positive-strand RNA viruses. BMV invaginates the outer nuclear membrane to form spherular VRCs. The investigators had previously demonstrated that a group of viruses promote host phosphatidylcholine synthesis at the viral replication sites for supporting viral replication. In particular, BMV replication protein 1a interacts with and recruits an enzyme of phosphatidylcholine biosynthesis to the VRCs. The recruitment of the enzyme will be blocked by disrupting the specific protein-protein interactions to achieve virus resistance without affecting host lipid synthesis. Because the lipid composition of host intracellular membranes is dynamic and complicated, an in vitro assay has been developed to examine how BMV replication protein 1a and similar viral replication proteins generate membrane invaginations of liposomes with defined lipid compositions. In addition, host protein Erv14 has been found to be required for BMV replication. The mechanism whereby Erv14 is involved in BMV VRC assembly and the possible involvement of Erv14 in the replication of other plant viruses will be determined.
