KSEF RDE: Screening of temperature sensitive and deletion libraries for host factors affecting virus replication

The estimated loss caused by plant viruses is tens of millions of dollars in Kentucky alone every year. Also, insect viruses are important pathogens of insects contributing to the control of various insect populations. These viruses greatly depend on co-opted host factors, thus identification of host factors is a major frontier in current research. Host factors could be novel targets of antiviral approaches that have several advantages over traditional viral targets, including broader antiviral effects against many related viruses and more durable antiviral effects. Efficient model systems, such as Tomato bushy stunt tombusvirus (TBSV) and the insect nodamuravirus (NoV) in combination with developing yeast as model host will promote rapid and .significant progress in our understanding of the roles of host factors in viral replication. This progress with TBSV and the animal NoV, in turn, will accelerate the advances with other viruses of humans and animals. TBSV and NoV are the system of choice for these studies, because efficient genome-wide screens in yeast will allow the PI to catalog host genes affecting replication in a genome-wide scale. The PI will use four unique screens with libraries currently only available for yeast. By extending the screens to NoV, for which the PI has adapted the yeast host, it will be possible to compare the host factors involved in replication of plant and insect viruses. Comparison of the sets of host factors affecting TBSV versus NoV replication will allow the PI to target those host factors that affect both viruses in future studies to obtain a broad antiviral strategy. The proposed work will likely lead to major new insights into virus replication and viral pathogenesis. This progress could lead to new antiviral approaches, identification of drug targets and broader antiviral activities.