Susan Weiss - June 24, 2020

Susan Weiss, PhD, Professor and Vice Chair, Department of Microbiology, Co-Director, Penn Center for Research on Coronaviruses and Other Emerging Pathogens, University of Pennsylvania School of Medicine, "Coronavirus antagonism of double stranded RNA induced antiviral pathways"

Professor Susan Weiss began work in the 1980s on the mouse hepatitis virus (MHV), a murine coronavirus, and is currently the co-director of the University of Pennsylvania Center of Research for Coronaviruses and Other Emerging Pathogens. In this talk she discusses work in her lab from the past few years on interferon antagonists encoded by lineage a (e.g. MHV) and lineage c (e.g. MERS) coronaviruses. Early on during infection, coronaviruses synthesize double stranded RNA which can be detected by host sensors. At least 3 pathways are involved in dsRNA detection: the OAS-RNase L pathway, the PKR pathway, and the MDA5-IFN (interferon) pathway. In the OAS-RNase L pathway, for example, several OAS proteins recognize dsRNA, which leads to RNase L dimerization/activation cleaving both viral and host RNA. This in turn inhibits protein synthesis and encourages apoptosis. Various studies from the lab have shown that coronaviruses encode multiple interferon antagonists in conserved nonstructural proteins and in lineage specific accessory proteins. In the murine coronavirus mouse model, both NS2 (an accessory protein) and EndoU (an enzyme) are required to prevent activation of OAS-RNase L, and the expression of both proteins is required for replication and pathogenesis in the liver but not in the brain. MERS-CoV, on the other hand, expresses two accessory proteins NS4a and NS4b that when deleted results in weak activation of RNAse L, IFN and ISGs (interferon stimulated genes) as well as PKR.