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Bine Wissendorf Simonsen

Two cGAS-like receptors induce antiviral immunity in Drosophila

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DOI

  • 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.

OriginalsprogEngelsk
TidsskriftNature
Vol/bind597
Sider (fra-til)114-118
Antal sider5
ISSN0028-0836
DOI
StatusUdgivet - sep. 2021

Bibliografisk note

Funding Information:
Acknowledgements We thank K. Slavik and P. Kranzusch for discussing and sharing information before publication; P. E. Andersen for help with generating Sting-knockout S2 cells; D. Obbard for providing Kallithea virus; and C. Meignin, J. Marques, J. Schneider and G. Haas for helpful discussions. R.H was supported by grants from the Novo Nordisk Foundation (NNF17OC0028184) and the Danish Council for Independent Research (4183-0032B and 0135-00338B). J.-L.I. was supported by Agence Nationale de la Recherche (ANR-17-CE15-0014), Investissement d’Avenir Programs (ANR-10-LABX-0036, ANR-11-EQPX-0022), Institut Universitaire de France and the Chinese National Overseas Expertise Introduction Center for Discipline Innovation (Project ‘111’ (D18010)). H.C was supported by the Natural Science Foundation (32000662) and the Foreign Experts Program (2020A1414010306). A.P. was supported by an ERC consolidator grant (ERC-CoG ProDAP, 817798) and grants from the German Research Foundation (PI 1084/5, TRR179 and TRR237).

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

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