2′3′-cGAMP triggers a STING- and NF-κB-dependent broad antiviral response in Drosophila
2′3′-cGAMP triggers a STING- and NF-κB-dependent broad antiviral response in Drosophila
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DOI：
10.1126/scisignal.abc4537
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发表时间：
2020-12-01
影响因子：
7.3
通讯作者：
Imler, Jean-Luc
中科院分区：
文献类型：
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作者：
Cai, Hua;Holleufer, Andreas;Imler, Jean-Luc
我们之前报道过，STING的一个直系同源物调控果蝇中细小核糖核酸病毒样病毒的感染。在哺乳动物中，STING被cGAS产生的环二核苷酸2'3'-cGAMP激活，cGAS作为胞质DNA的受体。在此，我们发现给果蝇注射2'3'-cGAMP可诱导dSTING调控基因的表达。将2'3'-cGAMP与一组RNA或DNA病毒共同注射，会导致病毒复制大幅减少。在Atg7和AGO2基因突变的果蝇中仍能观察到这种由2'3'-cGAMP介导的保护作用，Atg7和AGO2基因分别编码自噬和小干扰RNA途径的关键成分。相比之下，在编码NF - κB转录因子Relish的基因突变的果蝇中，这种保护作用消失。对注射2'3'-cGAMP的果蝇进行转录组分析，揭示了一种复杂的反应模式，其中基因被快速诱导、延迟诱导或持续诱导。我们的研究结果表明，dSTING调控一种依赖NF - κB的抗病毒程序，该程序早于脊椎动物中干扰素的出现。
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-kappa B 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-kappa B-dependent antiviral program that predates the emergence of interferons in vertebrates.