Description:

Talk Title: Decoding host antiviral defenses against diverse coronaviruses

Topic: “Adaptive and innate immune responses make unique contributions to host immunity against

coronavirus infection. When SARS-CoV-2 emerged, little was known about where antibodies bind to the virion during infection. To identify antibody binding sites, we developed a customized, phage-based mapping library to profile antibody responses to the full SARSCoV-2 proteome and found extensive antibody binding to non-RBD regions in Spike, and

other viral proteins. In studies assessing the population features that contribute to the elicitation of antibody responses against SARS-CoV-2, like age, we found a remarkable increase in antibody binding and ADCC activity in infants compared to adults in a unique mother-infant cohort suggesting a potential role for ADCC in age-dependent infection outcomes. Innate immunity, in particular the Type I Interferon (IFN) response, is another major contributor to coronavirus immunity. IFN signaling leads to the upregulation of hundreds of IFN stimulated genes (ISGs), some of which encode proteins with antiviral activity. The role of individual ISGs and their protein products in shaping infection outcomes across the family of human coronaviruses (HCoVs) is not known and requires comprehensive identification and mechanistic characterization of antiviral host proteins. We developed a CRISPR-Cas9 knockout screening platform to identify antiviral host

restriction factors against the mildly pathogenic HCoV-OC43 and are leveraging this screen technology to address critical questions about the specificity of restriction factors against diverse HCoVs. Additionally, we are combining biochemistry with high throughput approaches to understand the mechanisms of anti-HCoV host factors, like LY6E, that arose out of our screens. Overall, we hope to understand the fundamentals of host-coronavirus antiviral pathways and enhance our capacity to target ISGs in host-directed interventions.”