Elucidating the molecular mechanism by which bat Interferon Regulatory Factors 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 emerged in bats, evolved and then transmitted to humans. Bats are exceptional agents of zoonotic transmission - being virus reservoirs, remarkable virus shedders and phylogenetically close to humans. Although bats harbour many different viruses, they rarely show any 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 antiviral molecules called interferons (IFNs) and other conserved components of the innate immune system that form the first line of defence against pathogens. The main aim of our proposal will be to characterize IFN production and signaling 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 IFN production and/or signaling. Information from this proposal will be foundational for understanding the molecular mechanism by which bats adapt themselves to a multitude of viruses that can potentially cause future pandemics. Consequently, information from bat-virus immune co-evolution will provide a research framework for understanding human-virus co-evolution for the purpose of prevention, control, and possible eradication of new emerging viruses.