ABSTRACT
The fruitfly Drosophila melanogaster is a valuable model to unravel mechanisms of innate immunity, in particular in the context of viral infections. RNA interference, and more specifically the small interfering RNA pathway, is a major component of antiviral immunity in drosophila. In addition, the contribution of inducible transcriptional responses to the control of viruses in drosophila and other invertebrates is increasingly recognized. In particular, the recent discovery of a STING-IKKß-Relish signalling cassette in drosophila has confirmed that NF-κB transcription factors play an important role in the control of viral infections, in addition to bacterial and fungal infections. Here, we review recent developments in the field, which begin to shed light on the mechanisms involved in sensing of viral infections and in signalling leading to production of antiviral effectors.
Subject(s)
Drosophila Proteins/immunology , Drosophila melanogaster/immunology , Immunity, Innate/immunology , RNA Interference/immunology , Signal Transduction/immunology , Viruses/immunology , Animals , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Drosophila melanogaster/genetics , Drosophila melanogaster/virology , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , I-kappa B Kinase/genetics , I-kappa B Kinase/immunology , I-kappa B Kinase/metabolism , Immunity, Innate/genetics , Membrane Proteins/genetics , Membrane Proteins/immunology , Membrane Proteins/metabolism , RNA, Viral/genetics , RNA, Viral/immunology , RNA, Viral/metabolism , Signal Transduction/genetics , Transcription Factors/genetics , Transcription Factors/immunology , Transcription Factors/metabolism , Viruses/geneticsABSTRACT
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.