RRC ID 67268
Author Holleufer A, Winther KG, Gad HH, Ai X, Chen Y, Li L, Wei Z, Deng H, Liu J, Frederiksen NA, Simonsen B, Andersen LL, Kleigrewe K, Dalskov L, Pichlmair A, Cai H, Imler JL, Hartmann R.
Title Two cGAS-like receptors induce antiviral immunity in Drosophila.
Journal Nature
Abstract In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide (CDN) 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, present in both prokaryotes1 and eukaryotes2-5. In bacteria, these enzymes synthesize a range of cyclic oligonucleotide and have recently emerged as important regulators of phage infections6-8. Here, we identify two novel 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 dsRNA to produce the novel CDN 3'2'-cGAMP whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2' cGAMP in response to a yet unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors sensing different types of nucleic acids and triggering immunity through production of CDNs beyond 2'3'-cGAMP.
Volume 597(7874)
Pages 114-118
Published 2021-9-1
DOI 10.1038/s41586-021-03800-z
PII 10.1038/s41586-021-03800-z
PMID 34261128
MeSH Amino Acid Sequence Animals Cell Line Drosophila Proteins / metabolism Drosophila melanogaster / immunology* Drosophila melanogaster / metabolism Drosophila melanogaster / virology Female Humans Immunity, Innate / genetics Immunity, Innate / immunology Ligands Male Membrane Proteins / metabolism Models, Molecular NF-kappa B / metabolism Nucleotides, Cyclic / metabolism Nucleotidyltransferases / classification Nucleotidyltransferases / deficiency Nucleotidyltransferases / immunology* Nucleotidyltransferases / metabolism RNA, Double-Stranded / analysis RNA, Double-Stranded / immunology RNA, Double-Stranded / metabolism Receptors, Pattern Recognition / classification Receptors, Pattern Recognition / deficiency Receptors, Pattern Recognition / immunology Receptors, Pattern Recognition / metabolism* Viruses / immunology*
IF 42.779
Drosophila y1 w1118; attP2{nos-Cas9}/TM6C, Sb Tb [y+]