Elucidating the molecular mechanism by which bat IRFs modulate antiviral responses

Despite being one in every five mammalian species, bats are an under-studied species. Bats can host different viruses, many that can be transmitted to humans. SARS-CoV-2, the agent of the COVID-19 pandemic, is thought to have originated in bats. Bats are exceptional agents of zoonotic transmission - hosting many diverse viruses, having a remarkable capacity to shed virus, and being closely related to humans. Although bats carry many viruses, they rarely, if ever, show clinical signs of disease. This is likely because bats and viruses have co-evolved over thousands of years, leading to suitable adaptations in the bat immune system. Bats have the ability to produce protective anti-viral molecules called interferons (IFNs) and other conserved components of the innate immune system that form the first line of defense against pathogens. The main goal of our proposal is to characterize how IFN is made and how it functions in response to viral infection in bats. Our research will specifically study the role of three transcription factors (IRF3, IRF7 and IRF9) that are involved in the production and/or activity of IFN. Information from this proposal will be foundational for understanding the molecular mechanisms by which bats adapt to a multitude of viruses that can potentially cause future pandemics. Furthermore, understanding bat-virus co-evolution and the tricks bats use to protect themselves from viral infection will provide a research framework for understanding human-virus co-evolution, with the long-term goal of prevention, control, and possible eradication of emerging viruses.