Research Projects

The Type 1 Interferon (IFN-I) response is the most efficient anti-viral host mechanism, and viruses have evolved to suppress this response upon infection. The ongoing SARS-CoV2 pandemic is more dangerous and lethal than previous viral outbreaks, and understanding the interaction between host IFN-I response and SARS-CoV2 is a crucial topic in COVID-19 biology. Patient studies suggest defects in responsiveness to type I interferons are key in determining the severity of COVID-19. Low expression of IFNAR receptors in patients is associated with a life-threatening disease, while increased IFN-I response after infection could exacerbate pathology and disease. Depleting IRGM/Irgm1 results in constitutive upregulation of IFN-I response in cells and mice. The Irgm1 knockout (KO) mice are the only existing mice model with constitutive IFN-I response, making them the best model to understand whether inducing IFN-I response could be used as a prophylactic remedy in SARS-CoV2 or similar coronaviridae family infections in the future. To understand the interplay between IFN-I response and SARS-CoV2 infection, researchers have crossed hACE2 mice with Irgm1KO mice to obtain double transgenic mice (hACE2; Irgm1KO). These mice will be deficient in IFN-I response and can be infected with the SARS-CoV2 virus. This study will determine whether IRGM/Irgm1 is a good therapeutic target against SARS-CoV2.