2'3'-cGAMP triggers a STING- and NF-κB-dependent broad antiviral response in .
Fiche publication
Date publication
décembre 2020
Journal
Science signaling
Auteurs
Membres identifiés du Cancéropôle Est :
Pr IMLER Jean-Luc
Tous les auteurs :
Cai H, Holleufer A, Simonsen B, Schneider J, Lemoine A, Gad HH, Huang J, Huang J, Chen D, Peng T, Marques JT, Hartmann R, Martins NE, Imler JL
Lien Pubmed
Résumé
We previously reported that an ortholog of STING regulates infection by picorna-like viruses in In mammals, STING is activated by the cyclic dinucleotide 2'3'-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we showed that injection of flies with 2'3'-cGAMP induced the expression of dSTING-regulated genes. Coinjection of 2'3'-cGAMP with a panel of RNA or DNA viruses resulted in substantially reduced viral replication. This 2'3'-cGAMP-mediated protection was still observed in flies with mutations in and , genes that encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, this protection was abrogated in flies with mutations in the gene encoding the NF-κB transcription factor Relish. Transcriptomic analysis of 2'3'-cGAMP-injected flies revealed a complex response pattern in which genes were rapidly induced, induced after a delay, or induced in a sustained manner. Our results reveal that dSTING regulates an NF-κB-dependent antiviral program that predates the emergence of interferons in vertebrates.
Référence
Sci Signal. 2020 Dec 1;13(660):