WALS- George Khoury Lecture: Coronavirus Activation and Antagonism of Interferon Signaling Pathways: from MHV to SARS-CoV-2

Coronavirus interactions with the interferon signaling response are crucial for antiviral defense especially at the early stages of infection. Murine coronavirus, MHV, has taught us a lot about the basic biology of this family of viruses as well as antagonism of innate immune response, a hallmark of coronavirus infection. Building on our MHV data, we have more recently worked with human coronaviruses. We have optimized methods for comparing human coronaviruses in a primary nasal cell air liquid interface (ALI) culture system, which models the initial site of respiratory virus infection. Common cold coronaviruses as well as unrelated human rhinovirus exhibit early induction of interferon (IFN) signaling and IFN-mediated clearance, and preferential replication at nasal airway temperature (33 ยบ C) which confers muted host IFN responses. In contrast, lethal SARS-CoV-2 and MERS-CoV encode antagonist proteins that prevent IFN-mediated clearance. Our studies highlight nasal innate immune responses as predictive of infection outcomes and nasally-directed IFNs as potential therapeutics.For more information go tohttps://oir.nih.gov/wals/nih-directors-wednesday-afternoon-lecture-series-2023-2024/coronavirus-activation-antagonism-innate-immune-pathwaysAir date: 5/29/2024 2:00:00 PM
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