StemCell Therapy

STINGing viruses without interferon

The adaptor protein STING induces the production of antiviral interferons in response to the cyclic dinucleotide 23-cGAMP generated as a danger signal during viral infection of mammalian cells. Drosophila have a STING ortholog but do not produce interferons. Cai et al. found that exogenously administered 23-cGAMP protected Drosophila against multiple DNA and RNA viruses in a manner dependent on STING and the transcription factor Relish, an ortholog of NF-B. This antiviral immunity did not involve autophagy, a cellular process in which STING plays an evolutionarily conserved role and that can restrict viral replication, or RNA interference, an antiviral response in Drosophila. These results suggest that 23-cGAMP as a viral danger signal is evolutionarily older than previously suspected and that STING was incorporated into the interferon response during vertebrate evolution.

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 23-cGAMP produced by cGAS, which acts as a receptor for cytosolic DNA. Here, we showed that injection of flies with 23-cGAMP induced the expression of dSTING-regulated genes. Coinjection of 23-cGAMP with a panel of RNA or DNA viruses resulted in substantially reduced viral replication. This 23-cGAMPmediated 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-B transcription factor Relish. Transcriptomic analysis of 23-cGAMPinjected 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-Bdependent antiviral program that predates the emergence of interferons in vertebrates.

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23-cGAMP triggers a STING- and NF-Bdependent broad antiviral response in Drosophila - Science

This entry was posted on December 4, 2020 at 12:33 am and is filed under Molecular Genetics. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |