SARS-CoV-2 spike antagonizes innate antiviral immunity by targeting interferon regulatory factor 3

This article was originally published here

Front Cell Infect Microbiol. 2022 Jan 10;11:789462. doi: 10.3389/fcimb.2021.789462. eCollection 2021.

ABSTRACT

The pathogenesis of corona virus disease 2019 (COVID-19) is intimately linked to severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) and disease severity has been associated with compromised induction of cytokines of type I interferon (IFN-I) that coordinate the innate immune response to viral infections. Here, we identified the SARS-CoV-2-encoded protein, Spike, as an IFN-I inhibitor 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. Therefore, cells expressing SARS-CoV-2 Spike exhibited an increased RNA viral load compared to control cells. Co-immunoprecipitation experiments revealed that the SARS-CoV-2 Spike was associated with interferon regulatory factor 3 (IRF3), a key transcription factor that governs IFN-I activation. Co-expression analysis Going through immunoassays further indicated that Spike specifically suppressed IRF3 expression because levels of transcription factors NF-κB and STAT1 remained intact. Further biochemical experiments uncovered the SARS-CoV-2 Spike-potentiated proteasomal degradation of IRF3, implicating a novel mechanism by which SARS-CoV-2 evades the host’s innate antiviral immune response to facilitate the pathogenesis of COVID-19.

PMID:35083167 | PMC: PMC8785962 | DOI: 10.3389/fcimb.2021.789462

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