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Two cGAS-like receptors induce antiviral immunity in Drosophila.

Nature (2021-07-15)
Andreas Holleufer, Kasper Grønbjerg Winther, Hans Henrik Gad, Xianlong Ai, Yuqiang Chen, Lihua Li, Ziming Wei, Huimin Deng, Jiyong Liu, Ninna Ahlmann Frederiksen, Bine Simonsen, Line Lykke Andersen, Karin Kleigrewe, Louise Dalskov, Andreas Pichlmair, Hua Cai, Jean-Luc Imler, Rune Hartmann
ABSTRACT

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.

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3′,2′-Cgamp Disodium, ≥98% (HPLC)