Intellectual Merit: Replication is the central step in the infectious cycles of RNA viruses, which cause many devastating diseases in plants, animals and humans. These viruses replicate inside the infected cells by co-opting an unknown number of host proteins and reprogramming several cellular pathways. In spite of the significance of host proteins in viral pathogenesis, our current knowledge about host factors subverted for virus replication is incomplete. This project is aimed at addressing the role of the multifunctional host-coded translation elongation factor 1A (eEF1A), which is a permanent resident in the viral replicase complex and plays a key role in Tomato bushy stunt virus (TBSV) replication. The research will unravel the functions of eEF1A using innovative approaches including yeast and plant assays developed for tombusviruses, as well as the powerful cell-free TBSV replication assay in yeast extracts. This research will likely lead to major new insights into virus replication and viral pathogenesis and will have a considerable impact on our understanding of the mechanism that transforms the host cells into "viral factories". Since eEF1A likely affects replication of a large number of plant and animal viruses, major progress with tombusviruses would be highly advantageous to study of other viruses as well.

Broader Impacts: High school and undergraduate students will actively participate in the research. Students will be exposed to highly innovative research, thus providing them an invaluable learning experience. This research will promote interdisciplinary (plant pathology, biochemistry, cell biology, genetics) learning. The research also includes mentoring for postdoctoral researchers and preparing them for a scientific career in academia or industry. Pioneering research on tombusvirus replication will immensely help other scientists working with less tractable, but devastating viral pathogens for which similar studies are currently not yet feasible. Dissection of the role of eEF1A in viral pathogenesis and disease development will facilitate future antiviral approaches and treatments to reduce the effect of viral diseases in agriculture.

National Science Foundation (NSF)
Division of Molecular and Cellular Biosciences (MCB)
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Arcady Mushegian
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University of Kentucky
United States
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