Journal
SCIENCE SIGNALING
Volume 13, Issue 660, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.abc4537
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Funding
- ERA-NET Infect-ERA program [ANR-14-IFEC-0005]
- Agence Nationale de la Recherche [ANR-17-CE15-0014]
- Investissement d'Avenir Programs [ANR-10-LABX-0036, ANR-11-EQPX-0022]
- Chinese National Overseas Expertise Introduction Center for Discipline Innovation [Project 111] [D18010]
- CNRS
- INSERM
- Institut Universitaire de France
- Novo Nordisk foundation grant [NNF17OC0028184]
- Natural Science Foundation of Guangdong Province [2016A030310278]
- Science and Technology Planning Project of Guangzhou [201707010030]
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We previously reported that an ortholog of STING regulates infection by picorna-like viruses in Drosophila. 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 Atg7 and AGO2, 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-kappa B 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-kappa B-dependent antiviral program that predates the emergence of interferons in vertebrates.
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