Blocking RNA Virus Replication Through the Antiviral Functions of Cellular Helicases

Viruses are widespread pathogens causing many devastating diseases in plants, animals and humans. The PI lab has identified several hundreds of cellular factors that affect viral replication based on yeast model. A key discovery from the PI's work is the major roles of the co-opted cellular helicases in plant and insect virus replication. Progress in our understanding of the mechanisms of host factors is greatly accelerated by the use of easily tractable virus - host systems, such as Tomato bushy stunt virus (TBSV) and yeast model. The PI will identify and characterize the most potent cellular helicases to block plant and insect virus replication. Preliminary work with three cellular helicases showed complete block of viral replication in plant protoplasts, yeast cells and in vitro, thus justifying the potential of this novel approach. The following are the major strengths of the proposal: (i) Viral RNA replication is clearly of immense importance for viruses to infect living organisms. (ii) The combination of yeast and authentic cell-free assay developed by the PI is currently the most potent for studying the mechanism of host factors involvement in viral RNA replication and viral pathogenesis. (iii) This work has the potential to obtain a novel effective antiviral approach that has several advantages over traditional viral targets. The advantages include broader antiviral effects against many related and possibly even unrelated viruses and more durable antiviral effects. Developing an efficient antiviral strategy based on blocking viral replication via cellular helicases could rapidly be done in this elegant tombusvirus-yeast system. Based on the possible broad antiviral effect of these cellular helicases, which are highly conserved from plants to animals, research can then adapt the gained knowledge and methods for other animal, human and plant viruses. The research holds promise of benefiting society by leading to groundbreaking results in the area of virus replication, host-virus interactions and the adaptation of viruses to their hosts.