Article ; Online: Surface Proteins of SARS-CoV-2 Drive Airway Epithelial Cells to Induce IFN-Dependent Inflammation.
Journal of immunology (Baltimore, Md. : 1950)
2021 Volume 206, Issue 12, Page(s) 3000–3009
Abstract: ... CoV-2 surface proteins, particularly the understudied E protein, in driving cell specific inflammation ... that the SARS-CoV-2 surface proteins spike (S) and envelope (E) activate the key immune signaling IFN pathway ... on type I IFN signaling, specifically in lung epithelial cells. These findings underscore the role of SARS ...
| Abstract | SARS-CoV-2, the virus that has caused the COVID-19 pandemic, robustly activates the host immune system in critically ill patients. Understanding how the virus engages the immune system will facilitate the development of needed therapeutic strategies. In this study, we demonstrate both in vitro and in vivo that the SARS-CoV-2 surface proteins spike (S) and envelope (E) activate the key immune signaling IFN pathway in both human and mouse immune and epithelial cells independent of viral infection 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 patients. Induction of IFN signaling is dependent on canonical but discrepant inflammatory signaling mediators, as the activation induced by S is dependent on IRF3, TBK1, and MyD88, whereas that of E is largely MyD88 independent. Furthermore, these viral surface proteins, specifically E, induced peribronchial inflammation and pulmonary vasculitis 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, in driving cell specific inflammation and their potential for therapeutic intervention. |
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| MeSH term(s) | Animals ; Cell Line, Tumor ; Coronavirus Envelope Proteins/immunology ; Epithelial Cells/immunology ; Epithelial Cells/virology ; Female ; Humans ; Inflammation/immunology ; Interferon Type I/immunology ; Male ; Mice ; Spike Glycoprotein, Coronavirus/immunology |
| Chemical Substances | Coronavirus Envelope Proteins ; Interferon Type I ; Spike Glycoprotein, Coronavirus ; envelope protein, SARS-CoV-2 ; spike protein, SARS-CoV-2 |
| Language | English |
| Publishing date | 2021-06-02 |
| Publishing country | United States |
| Document type | Journal Article |
| ZDB-ID | 3056-9 |
| ISSN | 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381 |
| ISSN (online) | 1550-6606 |
| ISSN | 0022-1767 ; 1048-3233 ; 1047-7381 |
| DOI | 10.4049/jimmunol.2001407 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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