Two cGAS-like receptors induce antiviral immunity in Drosophila

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 prokaryotes(1) and eukaryotes(2-5). In bacteria, these enzymes synthesize a range of cyclic oligonucleotides and have recently emerged as important regulators of phage infections(6-8). Here we identify two cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting- and NF-kappa B-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.

Automated summary

In this study, two cGAS-like receptors (cGLR1 and cGLR2) were identified in the fruit fly Drosophila melanogaster, which activate antiviral immunity in response to RNA or DNA viruses. cGLR1 is activated by double-stranded RNA to produce 3'2'-cGAMP, while cGLR2 produces a combination of 2'3'-cGAMP and 3'2'-cGAMP in response to an unknown stimulus. This data establishes 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.