Ai Xianlong, Deng Huimin, Li Xiaoyan, Wei Ziming, Chen Yuqiang, Yin Ting, Zhang Junhui, Huang Jingxian, Li Haoming, Lin Xiaoqing, Tan Long, Chen Di, Zhang Xiaohan, Zhang Xiuqing, Meignin Carine, Imler Jean-Luc, Cai Hua
Sino-French Hoffmann Institute, State Key Laboratory of Respiratory Disease, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, China.
Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
Cell Rep. 2024 Dec 24;43(12):115081. doi: 10.1016/j.celrep.2024.115081. Epub 2024 Dec 16.
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.
环鸟苷酸腺苷酸合成酶样受体（cGLR）-干扰素基因刺激因子（STING）最近成为控制无脊椎动物病毒感染的重要途径。然而，其在机体水平的确切作用仍不清楚。在这里，我们使用STING::GFP敲入报告果蝇来记录该途径在体内的激活情况。四种组织对环状二核苷酸3'2'-环磷酸鸟苷-磷酸腺苷（cGAMP）的注射有强烈反应：中枢神经系统、中肠、马氏管和生殖导管。注射3'2'-cGAMP或感染两种具有不同嗜性的病毒的果蝇中STING::GFP的诱导模式表明，该报告基因是由病毒感染细胞产生的全身信号诱导的。因此，在脂肪体中异位表达cGLR2会在远处组织中诱导STING信号，并且在交配过程中，一种依赖于cGLR1/2的活性会传递给雌性。此外，病毒感染可以以依赖于cGLR1/2和STING的方式改变睡眠。总之，我们的结果揭示了环状二核苷酸信号在果蝇对病毒感染的全身宿主反应中的作用。
