Grant: Project Grant - PA: Pandemic Preparedness and Health Emergencies Research

Influenza A viruses (IAVs) are important pathogens for humans and animals. Innate immunity is the first line of the host defense system that detects and defenses against virus infection. Retinoic acid inducible gene-I (RIG-I) is one of the pattern recognition receptors and is essential for recognizing RNA virus infection. Upon recognition, RIG-I initiates signaling events rapidly, leading to the production of type I interferons and antiviral immunity. Our previous research identified RIG-I not only functions in the cytoplasm but also functions in the nucleus of the cells. This proposal will focus on how the cellular protein, RNA phosphatase regulates RIG-I mediated antiviral signaling in the context of IAV infection, how the viral protein antagonizes the RIG-I signaling to allow the virus to evade the immune responses, and the spatiotemporal dynamics of RIG-I mediated immune signaling in IAV infection. The study will provide insights into the development of novel RIG-I agonist- or antagonist- based therapeutics for viral infection.