The Virus-induced Cyclic Dinucleotide 2'3'-c-di-GMP Mediates STING-dependent Antiviral Immunity in Drosophila

Overview

Journal Immunity

Publisher Cell Press

Specialty Allergy & Immunology

Date 2023 Sep 2

PMID 37659413

Authors

Hua Cai

Lihua Li

Kailey M Slavik

Jingxian Huang

Ting Yin

Xianlong Ai

Lena Hedelin

Gabrielle Haas

Zhangmin Xiang

Yunyun Yang

Xiaoyan Li

Yuqiang Chen

Ziming Wei

Huimin Deng

Di Chen

Renjie Jiao

Nelson Martins

Carine Meignin

Philip J Kranzusch

Jean-Luc Imler

Affiliations

Soon will be listed here.

Abstract

In mammals, the enzyme cGAS senses the presence of cytosolic DNA and synthesizes the cyclic dinucleotide (CDN) 2'3'-cGAMP, which triggers STING-dependent immunity. In Drosophila melanogaster, two cGAS-like receptors (cGLRs) produce 3'2'-cGAMP and 2'3'-cGAMP to activate STING. We explored CDN-mediated immunity in 14 Drosophila species covering 50 million years of evolution and found that 2'3'-cGAMP and 3'2'-cGAMP failed to control infection by Drosophila C virus in D. serrata and two other species. We discovered diverse CDNs produced in a cGLR-dependent manner in response to viral infection in D. melanogaster, including 2'3'-c-di-GMP. This CDN was a more potent STING agonist than cGAMP in D. melanogaster and it also activated a strong antiviral transcriptional response in D. serrata. Our results shed light on the evolution of cGLRs in flies and provide a basis for understanding the function and regulation of this emerging family of pattern recognition receptors in animal innate immunity.

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