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The virus-induced cyclic dinucleotide 2′3′-c-di-GMP mediates STING-dependent antiviral immunity in Drosophila

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Cai, Hua | Li, Lihua | Slavik, Kailey M. | Huang, Jingxian | Yin, Ting | Ai, Xianlong | Hedelin, Léna | Haas, Gabrielle | Xiang, Zhangmin | Yang, Yunyun | Li, Xiaoyan | Chen, Yuqiang | Wei, Ziming | Deng, Huimin | Chen, Di | Jiao, Renjie | Martins, Nelson | Meignin, Carine | Kranzusch, Philip J. | Imler, Jean-Luc

Edité par CCSD ; Elsevier -

International audience. In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2030-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3020-cGAMP and 2030-cGAMP to activate STING. We explored CDN-mediated im- munity in 14 Drosophila species covering 50 million years of evolution and found that 2030-cGAMP and 3020-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discov- ered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2030-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity.

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