Wild-caught bats as a model to understand the evolution of virus-host interactions

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Bats are ecologically important as pollinators and insect controllers. They are also considered to be natural reservoirs for several emerging and re-emerging viruses that are causative agents of important human and agricultural infections. These viruses are speculated to have spilled over or “jumped” from bats to humans and other animals, directly or through intermediate hosts, causing severe and often fatal disease. Despite evidence of bats harboring up to hundreds of these viruses, they do not appear to show overt symptoms or clinical signs of infection. Little to nothing is understood why bats are not fully permissive to these viral infections and the physiological characteristics that allow them to be carriers or reservoirs of these viruses. Thus, bats provide an intriguing and relevant model system with which to study virus ecology and virus-host evolution. By understanding how bats control the pathology associated with virus infection, we can gain important insights into virus-host evolution, and leverage this knowledge for the construction of alternative anti-viral therapies, particularly for newly emerging virus that are linked with pandemics. ******This goal of this Discovery Grant is to generate a unique and innovative program that leverages the expertise of Dr. Mossman (virus-host interactions and innate immunity), Mr. Banerjee (viruses and bat host responses) and Dr. Faure (bat physiology) with the world's only bat colony containing wild caught and bred animals (McMaster Bat Lab). We propose to develop cell lines and tools with which to study mechanisms of virus bat interactions. In particular, we will focus on specific components of the host interferon response, the primary anti-viral response of mammals, for which we have preliminary data suggesting the response in bats differs significantly from that in humans. We will further develop an in vivo model system using Canadian big brown bats to study virus infection and subsequent intrinsic and innate responses in bats. As viral infections can alter host processes such as breeding, growth and development, it is important to understand dynamics of virus-bat interactions, as bats serve an important ecological role. Further, understanding how bats harbor and spread viruses has implications for disease control in animals and humans. As big brown bats naturally occur in Canada, our findings will directly impact the Canadian agricultural and health sectors. Moreover, findings will inform global strategies for disease control and development of novel antiviral therapies, particularly for new emerging viruses that bats appear to carry. Finally, this program will form the foundation for training of highly qualified personnel in a multidisciplinary environment.**