cGAS-like receptors drive a systemic STING-dependent host response in Drosophila
Xianlong Ai, Huimin Deng, Xiaoyan Li, Ziming Wei, Yuqiang Chen, Ting Yin, Junhui Zhang, Jingxian Huang, Haoming Li, Xiaoqing Lin, Long Tan, Di Chen, Xiaohan Zhang, Xiuqing Zhang, Carine Meignin, Jean‐Luc Imler, Hua Cai
Abstract
cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) recently emerged as an important pathway controlling viral infections in invertebrates. However, its exact contribution at the organismal level remains uncharacterized. Here, we use STING::GFP knockin reporter Drosophila flies to document activation of the pathway in vivo. Four tissues strongly respond to injection of the cyclic dinucleotide 3'2'- cyclic guanosine monophosphate-adenosine monophosphate (cGAMP): the central nervous system, midgut, Malpighian tubules, and genital ducts. The pattern of STING::GFP induction in flies injected with 3'2'-cGAMP or infected by two viruses with different tropism suggests that the reporter is induced by a systemic signal produced in virus-infected cells. Accordingly, ectopic expression of cGLR2 in the fat body induces STING signaling in remote tissues and a cGLR1/2-dependent activity is transferred to females during mating. Furthermore, viral infection can alter sleep in a cGLR1/2- and STING-dependent manner. Altogether, our results reveal a contribution of cyclic dinucleotide signaling to a systemic host response to viral infection in Drosophila.