In:
Science Signaling, American Association for the Advancement of Science (AAAS), Vol. 13, No. 660 ( 2020-12)
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1945-0877
,
1937-9145
DOI:
10.1126/scisignal.abc4537
Language:
English
Publisher:
American Association for the Advancement of Science (AAAS)
Publication Date:
2020
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