Journal
SCIENCE ADVANCES
Volume 6, Issue 38, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb4565
Keywords
-
Categories
Funding
- Spanish Ministry of Science, Innovation and Universities [SAF2015-67485-R, RTI2018-097581-B100]
- European Union (European Regional Development's Funds, FEDER) [SAF2015-67485-R, RTI2018-097581-B100]
- European Sequencing and Genotyping Infrastructure (Seventh Framework Programme) [262055]
- Wellcome Trust [051087/Z/97/Z, 058794/PMC/RW]
- UK Biotechnology and Biological Sciences Research Council [BB/M003647/1]
- BBSRC [BB/M003647/1] Funding Source: UKRI
Ask authors/readers for more resources
Cells contain numerous immune sensors to detect virus infection. The cyclic GMP-AMP (cGAMP) synthase (cGAS) recognizes cytosolic DNA and activates innate immune responses via stimulator of interferon genes (STING), but the impact of DNA sensing pathways on host protective responses has not been fully defined. We demonstrate that cGAS/STING activation is required to resist lethal poxvirus infection. We identified viral Schlafen (vSlfn) as the main STING inhibitor, and ectromelia virus was severely attenuated in the absence of vSlfn. Both vSlfn-mediated virulence and STING inhibitory activity were mapped to the recently discovered poxin cGAMP nuclease domain. Animals were protected from subcutaneous, respiratory, and intravenous infection in the absence of vSlfn, and interferon was the main antiviral protective mechanism controlled by the DNA sensing pathway. Our findings support the idea that manipulation of DNA sensing is an efficient therapeutic strategy in diseases triggered by viral infection or tissue damage-mediated release of self-DNA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available