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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.celrep.2023.112179DOI Listing

Publication Analysis

Top Keywords

mitochondrial dna
8
response noroviruses
8
cgas-sting pathway
8
interferon response
8
norovirus-infected cells
8
cgas ifi16
8
dna
6
leaked genomic
4
genomic mitochondrial
4
dna contribute
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!