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Two cGAS-like receptors induce antiviral immunity in Drosophila

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  • Andreas Holleufer
  • ,
  • Kasper Grønbjerg Winther
  • Hans Henrik Gad
  • Xianlong Ai, Guangzhou Medical College
  • ,
  • Yuqiang Chen, Guangzhou Medical College
  • ,
  • Lihua Li, Guangzhou Medical College
  • ,
  • Ziming Wei, Guangzhou Medical College
  • ,
  • Huimin Deng, Guangzhou Medical College
  • ,
  • Jiyong Liu, Guangzhou Medical College
  • ,
  • Ninna Ahlmann Frederiksen
  • ,
  • Bine Simonsen
  • Line Lykke Andersen, Technical University of Munich
  • ,
  • Karin Kleigrewe, Technical University of Munich
  • ,
  • Louise Dalskov
  • Andreas Pichlmair, Technical University of Munich, German Center for Infection Research (DZIF)
  • ,
  • Hua Cai, Guangzhou Medical College
  • ,
  • Jean Luc Imler, Université de Strasbourg, Guangzhou Medical College
  • ,
  • Rune Hartmann

In mammals, cyclic GMP–AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2′3′-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is present in both prokaryotes1 and eukaryotes2–5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotides and have recently emerged as important regulators of phage infections6–8. Here we identify two cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting- and NF-κB-dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by double-stranded RNA to produce the cyclic dinucleotide 3′2′-cGAMP, whereas cGLR2 produces a combination of 2′3′-cGAMP and 3′2′-cGAMP in response to an as-yet-unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors that sense different types of nucleic acids and trigger immunity through the production of cyclic dinucleotides beyond 2′3′-cGAMP.

Original languageEnglish
JournalNature
Volume597
Pages (from-to)114-118
Number of pages5
ISSN0028-0836
DOIs
Publication statusPublished - Sep 2021

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© 2021, The Author(s), under exclusive licence to Springer Nature Limited.

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