Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex
© 2023. The Author(s)..
Currently, the incidence and fatality rate of SARS-CoV-2 remain continually high worldwide. COVID-19 patients infected with SARS-CoV-2 exhibited decreased type I interferon (IFN-I) signal, along with limited activation of antiviral immune responses as well as enhanced viral infectivity. Dramatic progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing pathways. However, it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during infection. In the current study, we figure out that SARS-CoV-2 infection leads to the accumulation of released mitochondria DNA (mtDNA), which in turn triggers cGAS to activate IFN-I signaling. As countermeasures, SARS-CoV-2 nucleocapsid (N) protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I signaling. Mechanically, N protein disrupts the assembly of cGAS with its co-factor G3BP1 by undergoing DNA-induced liquid-liquid phase separation (LLPS), subsequently impairs the double-strand DNA (dsDNA) detection ability of cGAS. Taken together, our findings unravel a novel antagonistic strategy by which SARS-CoV-2 reduces DNA-triggered IFN-I pathway through interfering with cGAS-DNA phase separation.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Signal transduction and targeted therapy - 8(2023), 1 vom: 26. Apr., Seite 170 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Cai, Sihui [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 27.10.2023 Date Revised 27.10.2023 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41392-023-01420-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356044238 |
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| 245 | 1 | 0 | |a Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex |
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| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a Currently, the incidence and fatality rate of SARS-CoV-2 remain continually high worldwide. COVID-19 patients infected with SARS-CoV-2 exhibited decreased type I interferon (IFN-I) signal, along with limited activation of antiviral immune responses as well as enhanced viral infectivity. Dramatic progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing pathways. However, it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during infection. In the current study, we figure out that SARS-CoV-2 infection leads to the accumulation of released mitochondria DNA (mtDNA), which in turn triggers cGAS to activate IFN-I signaling. As countermeasures, SARS-CoV-2 nucleocapsid (N) protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I signaling. Mechanically, N protein disrupts the assembly of cGAS with its co-factor G3BP1 by undergoing DNA-induced liquid-liquid phase separation (LLPS), subsequently impairs the double-strand DNA (dsDNA) detection ability of cGAS. Taken together, our findings unravel a novel antagonistic strategy by which SARS-CoV-2 reduces DNA-triggered IFN-I pathway through interfering with cGAS-DNA phase separation | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Zhang, Chenqiu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhuang, Zhen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shengnan |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Ling |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Shuai |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zheyu |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Weihong |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Shouheng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Jincun |e verfasserin |4 aut | |
| 700 | 1 | |a Guan, Xiangdong |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Jianfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Yaoxing |e verfasserin |4 aut | |
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