Pathogenesis and Evolution of Influenza A Viruses in Swine

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The overarching goal of my research program is to understand the impact of the genetic, epidemiological and environmental factors that drive influenza A virus (IAV) evolution and the biological consequences of these changes in one of its natural hosts. The long-term aims of my research program are: Identify genetic factors associated with virulence and the ability of a virus to be endemically sustained within a population. Determine individual and population level consequences of and contributions to the evolution of influenza viruses in swine and vice versa.Leading up to this proposal, I have been collecting IAVs from pigs through my ongoing surveillance activities in Western Canada. These IAV isolates from pigs and their sequences along with related environmental and epidemiological data (e.g., morbidity and mortality information, previous infections with flu and other diseases, housing status, and production status) provide a basis for the proposed work and will continue to contribute to my research program.The fundamental biological questions on evolutionary drive and the resulting alterations in the biological properties of IAVs will be addressed through short-term objectives that will: 1) Determine evolutionary relationships of IAVs; and 2) Discover the effects of naturally occurring amino acid (AA) insertions and deletions on the biological properties of the IAVs through in-vitro, ex-vivo and in-vivo experiments. Research is lacking that answers the fundamental biological questions on how environmental, epidemiological and host pressures drive genetic change in swine IAVs and how these changes result in alterations in the biological properties of the virus within its natural host. For as much as IAVs have been studied over the last century, there are still many questions to answer.My expertise of influenza in pigs makes me uniquely qualified to answer these questions and to train the next generation of highly qualified personnel. In addition to my influenza expertise, I am also a veterinary pathologist with access to swine farms, swine veterinarians and other diagnosticians. This has allowed me the opportunity to establish a network for collection and characterization of IAVs from pigs, and to discover new viruses in pigs. My research program will develop novel approaches with a strong scientific foundation for assessing virulence and pathogenesis of influenza viruses that will involve undergraduate and graduate students, and post-doctoral fellows in basic and innovative techniques in virology and molecular biology, and answer compelling questions about how influenza viruses evolve and cause disease.