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Viral cGAMP nuclease reveals the essential role of DNA sensing in protection against acute lethal virus infection

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Item Type:Article
Title:Viral cGAMP nuclease reveals the essential role of DNA sensing in protection against acute lethal virus infection
Creators Name:Hernáez, B. and Alonso, G. and Georgana, I. and El-Jesr, M. and Martín, R. and Shair, K.H.Y. and Fischer, C. and Sauer, S. and Maluquer de Motes, C. and Alcamí, A.
Abstract: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.
Keywords:Animals, Mice
Source:Science Advances
ISSN:2375-2548
Publisher:American Association for the Advancement of Science
Volume:6
Number:38
Page Range:eabb4565
Date:18 September 2020
Official Publication:https://doi.org/10.1126/sciadv.abb4565
PubMed:View item in PubMed

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