Journal Article

Two cGAS-like receptors induce antiviral immunity in Drosophila

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

2021

Overview

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-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. Two cGAS-like receptors, cGLR1 and cGLR2, identified in Drosophila melanogaster are shown to induce antiviral immunity in response to RNA or DNA virus infections through the production of 2′3′-cGAMP and 3′2′-cGAMP.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/250/254 / 631/250/262/2106 / 631/326/596/2557 / Amino Acid Sequence / Animals / Antiviral drugs / Binding sites / Cell Line / Cyclic GMP / Deoxyribonucleic acid / DNA / DNA viruses / Double-stranded RNA / Drosophila melanogaster - immunology / Drosophila melanogaster - metabolism / Drosophila melanogaster - virology / Drosophila Proteins - metabolism / Enzymes / Female / Fruit flies / Genes / Humanities and Social Sciences / Humans / Immune response / Immune system / Immunity / Immunity, Innate - genetics / Immunity, Innate - immunology / Immunology / Infections / Innate immunity / Insects / Kinases / Life Sciences / Ligands / Male / Membrane Proteins - metabolism / Models, Molecular / multidisciplinary / Mutation / NF-kappa B - metabolism / NF-κB protein / Nucleic acids / Nucleotides, Cyclic - metabolism / Nucleotidyltransferases - classification / Nucleotidyltransferases - deficiency / Nucleotidyltransferases - immunology / Nucleotidyltransferases - metabolism / Oligonucleotides / Pathogens / Pattern recognition / Phages / Receptors / Receptors, Pattern Recognition - classification / Receptors, Pattern Recognition - deficiency / Receptors, Pattern Recognition - immunology / Receptors, Pattern Recognition - metabolism / Ribonucleic acid / RNA / RNA viruses / RNA, Double-Stranded - analysis / RNA, Double-Stranded - immunology / RNA, Double-Stranded - metabolism / Science / Science (multidisciplinary) / Viral infections / Viruses / Viruses - immunology