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HGNC Genes

SARS-CoV-2 proteins

ProteinS (1)

ProteinE (1)


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    Surface proteins of SARS-CoV-2 drive airway epithelial cells to induce interferon-dependent inflammation MESHD

    Authors: Gautam Anand; Alexandra M Perry; Celeste L Cummings; Emma St. Raymond; Regina A Clemens; Ashley L Steed

    doi:10.1101/2020.12.14.422710 Date: 2020-12-14 Source: bioRxiv

    SARS-CoV-2, the virus that has caused the COVID-19 pandemic MESHD, robustly activates the host immune system in critically ill MESHD patients. Understanding how the virus engages the immune system will facilitate the development of needed therapeutic strategies. Here we demonstrate both in vitro and in vivo that the SARS-CoV-2 surface proteins Spike (S PROTEIN) and Envelope (E) activate the key immune signaling interferon (IFN) pathway in both immune and epithelial cells independent of viral infection MESHD and replication. These proteins induce reactive oxidative species generation and increases in human and murine specific IFN-responsive cytokines and chemokines, similar to their upregulation in critically ill COVID-19 MESHD patients. Induction of IFN signaling is dependent on canonical but discrepant inflammatory signaling mediators as the activation induced by S is dependent on IRF3 HGNC, TBK1 HGNC, and MYD88 HGNC while that of E is largely MYD88 HGNC independent. Furthermore, these viral surface proteins, specifically E, induced peribronchial inflammation MESHD and pulmonary vasculitis MESHD in a mouse model. Finally we show that the organized inflammatory infiltrates are dependent on type I IFN signaling, specifically in lung epithelial cells. These findings underscore the role of SARS-CoV-2 surface proteins, particularly the understudied E protein PROTEIN, in driving cell specific inflammation MESHD and their potential for therapeutic intervention. Author SummarySARS-CoV-2 robustly activates widespread inflammation MESHD, but we do not understand mechanistically how the virus engages the immune system. This knowledge will facilitate the development of critically needed therapeutic strategies to promote beneficial immune responses will dampening harmful inflammation MESHD. Here we demonstrate that SARS-CoV-2 surface proteins spike PROTEIN and envelope alone activated innate cell function and the interferon signaling pathway. This activation occurred in both immune and epithelial cells, and mechanistic studies demonstrated dependence on known key inflammatory signaling mediators, IRF3 HGNC, TBK1 HGNC, and MYD88 HGNC. In animal studies, we showed that these viral surface proteins induce epithelial cell IFN-dependent lung pathology, reminiscent to acute COVID-19 MESHD pulmonary infection MESHD. These findings underscore the need for further investigation into the role of SARS-CoV-2 surface proteins, particularly the understudied E protein PROTEIN, in driving cell specific inflammation MESHD.

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MeSH Disease
HGNC Genes
SARS-CoV-2 Proteins


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