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Leaked genomic and mitochondrial DNA contribute to the host response to noroviruses in a STING-dependent manner.

Published version
Peer-reviewed

Repository DOI


Type

Article

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Authors

Jahun, Aminu S 
Sorgeloos, Frederic 
Chaudhry, Yasmin 
Arthur, Sabastine E 
Hosmillo, Myra 

Abstract

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.

Description

Keywords

CP: Immunology, CP: Molecular biology, DNA leakage, IFI16, NS4, STING, VF1, cGAS, cytosolic DNA, genomic DNA, interferon response, mitochondrial DNA, norovirus, p204, DNA, Mitochondrial, Genomics, Immunity, Innate, Interferons, Nucleotidyltransferases, Signal Transduction, Membrane Proteins

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (207498/Z/17/Z)
Wellcome Trust (207498/Z/17/Z)
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2023-10-23 15:03:06
Published version added
2023-02-14 00:30:34
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