Nov 27, 2019

2'3'-cGAMP triggers a STING and NF-κB dependent broad antiviral response in Drosophila

BioRxiv : the Preprint Server for Biology
Hua CaiJean-Luc Imler


We recently reported that an orthologue 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 show that injection of flies with 2'3'-cGAMP can induce expression of dSTING-regulated genes. Co-injection of 2'3'-cGAMP with a panel of RNA or DNA viruses results in significant reduction of viral replication. This 2'3'-cGAMP-mediated protection is still observed in flies mutant for the genes Atg7 and AGO2, which encode key components of the autophagy and small interfering RNA pathways, respectively. By contrast, it is abrogated in flies mutant for the NF-κB transcription factor Relish. Analysis of the transcriptome of 2'3'-cGAMP injected flies reveals a complex pattern of response, with early and late induced genes. Our results reveal that dSTING regulates an NF-κB -dependent antiviral program, which predates the emergence of Interferon Regulatory Factors and interferons in vertebrates.

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Mentioned in this Paper

Interferon Regulatory Factors
Cyclic Peptides
EIF2C2 protein, human
ATG7 gene

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