Viral cGAMP nuclease reveals the essential role of DNA sensing in protection against acute lethal virus infection
In: Digital.CSIC. Repositorio Institucional del CSIC instname Science Advances; (2020)
Online
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Zugriff:
DNA sensing inhibition by viral cGAMP nuclease impairs anti-viral responses and protective immunity.
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.
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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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Autor/in / Beteiligte Person: | El-Jesr, Misbah ; Hernáez, Bruno ; Fischer, Cornelius ; Alcami, Antonio ; Sauer, Sascha ; Shair, Kathy H. Y. ; Georgana, Iliana ; Martín, Rocío ; Alonso, Graciela ; Carlos Maluquer de Motes ; Ministerio de Ciencia, Innovación y Universidades (España) ; Commission, European ; Biotechnology and Biological Sciences Research Council (UK) |
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Quelle: | Digital.CSIC. Repositorio Institucional del CSIC instname Science Advances; (2020) |
Veröffentlichung: | American Association for the Advancement of Science, 2020 |
Medientyp: | unknown |
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