This project will study how cells infected by one virus become resistant to a secondary infection by the same or closely related virus. This process, called superinfection exclusion (SIE), is used by many viruses, including important pathogens of humans, animals, and plants; it plays an important role in the pathogenesis and evolution of viral populations and has clear implications for treating viral infections. For instance, in plants, purposeful inoculation with a harmless virus strain can be used to protect plants from infection by related pathogenic viruses. In spite of its significance, the phenomenon of SIE is not well understood. Thus, elucidation of the SIE mechanism(s) should have broad scientific impact by providing a necessary foundation for development of new strategies to control viral diseases of humans and economically important agricultural crops. The research will also have strong educational impact by offering training opportunities for postdoctoral researchers, graduate and undergraduate students and by developing tools that can be used for promoting STEM learning by younger students.
This research project aims to elucidate the mechanism of SIE of Citrus tristeza virus (CTV), a member of the family Closteroviridae, which includes the largest and most complex positive-strand RNA viruses of higher plants. CTV represents a valuable model system for studying SIE, due to the existence of numerous well-characterized isolates with distinctive genetic characteristics. Furthermore, CTV provides a possibility for studying this phenomenon at the whole organism level. The project builds on observations suggesting that SIE by CTV operates by a unique mechanism, which involves multiple virus-encoded factors. Advanced genetic tools will be combined with innovative techniques and ultrastructural approaches for studying protein-protein and RNA-protein interactions. Materials and data produced by the project will be openly accessible for research and educational uses. For example, the fluorescently-tagged viruses used as part of the research enable visualization of virus movement in infected trees and thus serve as an excellent learning tool for engaging young students. Taken together, the results of the research are expected to produce new insights into the mechanism of SIE by CTV, as well as to advance understanding of virus-host interactions.
