Diseases caused by plant viruses lead to diminished food quantity and quality, which in turn, have had devastating economic, social, political or historical consequences. In order to replicate or to be transported in host cells, viruses must divert, commandeer, or inhibit cellular functions to their advantage while concomitantly avoiding defense responses mounted by the host. Ultimately, successful infection of cells by viruses is a consequence of the complex integration of altered host gene expression, protein-protein interactions and induced changes in protein sub-cellular localization. Characterization of these processes using systems biology approaches requires as comprehensive a view of host-virus protein interaction and localization. This project will employ advanced fluorescence microscopy techniques in conjunction with high-resolution protein interaction screens, based upon yeast two-hybrid technology, in order to identify host factors that interact with proteins encoded by the genomes of plant rhabdoviruses. These studies are critical for fulfilling the long-term research goal of understanding how host and viral factors function in concert at the molecular level leading to disease. The intellectual merit of the proposed research lies in the fact that it will contribute to an understanding of how pathogens evade host defense responses while establishing compatible interactions. In turn, the wealth of information generated in this project may provide the basis for the development of novel anti-viral strategies. Additionally, the project will have a broader impact as novel resources will be generated that will benefit the plant biology community in general, and in particular those that use Nicotiana benthamiana, which has emerged as a highly significant model host for plant pathogens, particularly viruses. Furthermore, the project will provide multidisciplinary training for postdoctoral scholars, graduate and undergraduate students, potentially recruited from underrepresented and minority populations, in microscopy-, molecular- and computer-based analyses.
