Leaked genomic and mitochondrial DNA contribute to the host response to noroviruses in a STING-dependent manner
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved..
The cGAS-STING pathway is central to the interferon response against DNA viruses. However, recent studies are increasingly demonstrating its role in the restriction of some RNA viruses. Here, we show that the cGAS-STING pathway also contributes to the interferon response against noroviruses, currently the commonest causes of infectious gastroenteritis worldwide. We show a significant reduction in interferon-β induction and a corresponding increase in viral replication in norovirus-infected cells after deletion of STING, cGAS, or IFI16. Further, we find that immunostimulatory host genome-derived DNA and mitochondrial DNA accumulate in the cytosol of norovirus-infected cells. Lastly, overexpression of the viral NS4 protein is sufficient to drive the accumulation of cytosolic DNA. Together, our data find a role for cGAS, IFI16, and STING in the restriction of noroviruses and show the utility of host genomic DNA as a damage-associated molecular pattern in cells infected with an RNA virus.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
Cell reports - 42(2023), 3 vom: 28. März, Seite 112179 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Jahun, Aminu S [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.04.2023 Date Revised 10.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2023.112179 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Jahun, Aminu S |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Leaked genomic and mitochondrial DNA contribute to the host response to noroviruses in a STING-dependent manner |
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| 500 | |a Date Revised 10.04.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a The cGAS-STING pathway is central to the interferon response against DNA viruses. However, recent studies are increasingly demonstrating its role in the restriction of some RNA viruses. Here, we show that the cGAS-STING pathway also contributes to the interferon response against noroviruses, currently the commonest causes of infectious gastroenteritis worldwide. We show a significant reduction in interferon-β induction and a corresponding increase in viral replication in norovirus-infected cells after deletion of STING, cGAS, or IFI16. Further, we find that immunostimulatory host genome-derived DNA and mitochondrial DNA accumulate in the cytosol of norovirus-infected cells. Lastly, overexpression of the viral NS4 protein is sufficient to drive the accumulation of cytosolic DNA. Together, our data find a role for cGAS, IFI16, and STING in the restriction of noroviruses and show the utility of host genomic DNA as a damage-associated molecular pattern in cells infected with an RNA virus | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CP: Immunology | |
| 650 | 4 | |a CP: Molecular biology | |
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| 650 | 4 | |a NS4 | |
| 650 | 4 | |a STING | |
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| 650 | 4 | |a genomic DNA | |
| 650 | 4 | |a interferon response | |
| 650 | 4 | |a mitochondrial DNA | |
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| 700 | 1 | |a Sorgeloos, Frederic |e verfasserin |4 aut | |
| 700 | 1 | |a Chaudhry, Yasmin |e verfasserin |4 aut | |
| 700 | 1 | |a Arthur, Sabastine E |e verfasserin |4 aut | |
| 700 | 1 | |a Hosmillo, Myra |e verfasserin |4 aut | |
| 700 | 1 | |a Georgana, Iliana |e verfasserin |4 aut | |
| 700 | 1 | |a Izuagbe, Rhys |e verfasserin |4 aut | |
| 700 | 1 | |a Goodfellow, Ian G |e verfasserin |4 aut | |
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