%0 Generic %A Xiong, Qingqing %A Huang, Hongjun %A Wang, Ning %A Chen, Ruoyu %A Chen, Naiyang %A Han, Honghui %A Wang, Qin %A Siwko, Stefan %A Liu, Mingyao %A Qian, Min %A Du, Bing %D 2018 %T Table_1_Metabolite-Sensing G Protein Coupled Receptor TGR5 Protects Host From Viral Infection Through Amplifying Type I Interferon Responses.XLSX %U https://frontiersin.figshare.com/articles/dataset/Table_1_Metabolite-Sensing_G_Protein_Coupled_Receptor_TGR5_Protects_Host_From_Viral_Infection_Through_Amplifying_Type_I_Interferon_Responses_XLSX/7156388 %R 10.3389/fimmu.2018.02289.s001 %2 https://frontiersin.figshare.com/ndownloader/files/13169990 %K TGR5 %K ISG %K metabolite-sensing GPCRs %K IFN-I %K viral infection %X

The metabolite-sensing G protein–coupled receptors (GPCRs) bind to various metabolites and transmit signals that are important for proper immune and metabolic functions. However, the roles of metabolite-sensing GPCRs in viral infection are not well characterized. Here, we identified metabolite-sensing GPCR TGR5 as an interferon (IFN)-stimulated gene (ISG) which had increased expression following viral infection or IFN-β stimulation in a STAT1-dependent manner. Most importantly, overexpression of TGR5 or treatment with the modified bile acid INT-777 broadly protected host cells from vesicular stomatitis virus (VSV), newcastle disease virus (NDV) and herpes simplex virus type 1 (HSV-1) infection. Furthermore, VSV and HSV-1 replication was increased significantly in Tgr5-deficient macrophages and the VSV distribution in liver, spleen and lungs was increased in Tgr5-deficient mice during VSV infection. Accordingly, Tgr5-deficient mice were much more susceptible to VSV infection than wild-type mice. Mechanistically, TGR5 facilitates type I interferon (IFN-I) production through the AKT/IRF3-signaling pathway, which is crucial in promoting antiviral innate immunity. Taken together, our data reveal a positive feedback loop regulating IRF3 signaling and suggest a potential therapeutic role for metabolite-sensing GPCRs in controlling viral diseases.

%I Frontiers