Recently, the research team of Liu Cuihua of the Institute of Microbiology of the Chinese Academy of Sciences and the research team of Zhang Lingqiang, Institute of Military Medical Sciences, Academy of Military Sciences, published an article entitled "A Golgi-resident GPR108 cooperates with E3 ubiquitin ligase Smurf1 to suppress antiviral innate immunity" in Cell Reports. This study revealed a novel mechanism by which Golgi localization protein GPR108 and E3 ubiquitin ligase Smurf1 synergistically inhibit antiviral innate immunity.

Figure 1. Golgi localization protein GPR108 in combination with ubiquitin ligase Smurf1 inhibits antiviral immunity

The researchers screened 59 predicted Golgi locator proteins and found that GPR108 expression was significantly upregulated after viral infection, suggesting that GPR108 may have important regulatory functions during viral infection. The results of GPR108 knockout cell experiments proved that GPR108 can inhibit the type I interferon response induced by viral infection. Further mechanistic exploration found that viral infection could induce GPR108 to bind to the C2 domain of E3 ubiquitin ligase Smurf1, thereby undoing Smurf1 homodimer-mediated self-inhibition and activating Smurf1. Activated Smurf1 promotes the binding of phosphorylated IRF3 to the autophagy receptor NDP52 by promoting its K63 ubiquitination modification of phosphorylated IRF3, ultimately promoting autophagy degradation of IRF3. The researchers also further demonstrated that GPR108 can suppress the antiviral innate immune response through mouse virus infection models

The study revealed a novel mechanism by which the Golgi localization protein GPR108 inhibits the antiviral innate immune response. This finding provides new insights into the fine regulatory mechanism of Golgi apparatus in antiviral immune responses, and suggests that the GPR108-Smurf1 axis may be a potential new target for intervention to alleviate histopathological damage caused by excessive inflammation in antiviral immune responses. 

Zhao Mengyuan, a master's student from the Institute of Microbiology, Chinese Academy of Sciences, and a visiting graduate student Daniel Zhang are the co-first authors of the paper, and Liu Cuihua, a researcher at the Institute of Microbiology, Chinese Academy of Sciences, and Zhang Lingqiang, a researcher at the Institute of Military Medical Sciences and the National Center for Protein Science (Beijing), are the co-corresponding authors of this paper. The research was supported by the National Key R&D Program of China, the National Natural Science Foundation of China, the Strategic Leading Science and Technology Project (Class B) of the Chinese Academy of Sciences, and the Independent Project Fund of the State Key Laboratory of Proteomics. 

Source: AutophagyAdvances, Virology Community