Corona virus disease 2019 (COVID-19) pathogenesis is intimately linked to the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and disease severity has been associated with compromised induction of type I interferon (IFN-I) cytokines which coordinate the innate immune response to virus infections. Here we identified the SARS-CoV-2 encoded protein, Spike, as an inhibitor of IFN-I that antagonizes viral RNA pattern recognition receptor RIG-I signaling. Ectopic expression of SARS-CoV-2 Spike blocked RIG-I mediated activation of IFNβ and downstream induction of interferon stimulated genes. Consequently, SARS-CoV-2 Spike expressing cells harbored increased RNA viral burden compared to control cells. Co-immunoprecipitation experiments revealed SARS-CoV-2 Spike associated with interferon regulatory factor 3 (IRF3), a key transcription factor that governs IFN-I activation. Co-expression analysis via immunoassays further indicated Spike specifically suppressed IRF3 expression as NF-κB and STAT1 transcription factor levels remained intact. Further biochemical experiments uncovered SARS-CoV-2 Spike potentiated proteasomal degradation of IRF3, implicating a novel mechanism by which SARS-CoV-2 evades the host innate antiviral immune response to facilitate COVID-19 pathogenesis.
【저자키워드】 SARS-CoV-2, Innate immunity, interferon, IRF3, RIG-I antiviral, 【초록키워드】 COVID-19, Co-expression analysis, ectopic expression, Corona virus, Cytokines, Pathogenesis, innate immune response, spike, disease severity, interferon, cytokine, virus, type I interferon, RNA, Pattern recognition, immunoassays, Protein, immunoassay, infections, Viral, COVID-19 pathogenesis, cells, IFN-I, IRF3, RIG-I, Viral RNA, experiment, Stat1, respiratory, inhibitor, disease, expression, mechanism, virus infections, SARS-CoV-2 spike, NF-κB, Signaling, Analysis, pattern recognition receptor, transcription factor, Virus Disease, antiviral immune response, acute respiratory syndrome, Activation, biochemical, interferon regulatory factor, Severe Acute Respiratory Syndrome Corona Virus, IFNβ, viral burden, downstream, control cells, proteasomal degradation, Host, Genes, Cell, stimulated, blocked, indicated, remained, facilitate, suppressed, evade, expressing, expression of SARS-CoV-2, the SARS-CoV-2, 【제목키워드】 spike, Innate, Factor, targeting,