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

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  • Hua Cai, Guangzhou Medical College, Université de Strasbourg
  • ,
  • Andreas Holleufer
  • Bine Simonsen
  • Juliette Schneider, Université de Strasbourg
  • ,
  • Aurélie Lemoine, Université de Strasbourg
  • ,
  • Hans Henrik Gad
  • Jingxian Huang, Guangzhou Medical College
  • ,
  • Jieqing Huang, Guangzhou Medical College
  • ,
  • Di Chen, Guangzhou Medical College
  • ,
  • Tao Peng, Guangzhou Medical College
  • ,
  • João T. Marques, Université de Strasbourg, Universidade Federal de Minas Gerais
  • ,
  • Rune Hartmann
  • Nelson E. Martins, Université de Strasbourg
  • ,
  • Jean Luc Imler, Guangzhou Medical College, Université de Strasbourg

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-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.

Original languageEnglish
Article numbereabc4537
JournalScience Signaling
Volume13
Issue660
Number of pages12
ISSN1945-0877
DOIs
Publication statusPublished - Dec 2020

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