USP39 promotes antiviral defense through post-transcriptional control of RIG-I and stabilization of STING

by Jiazheng Quan, Xibao Zhao, Shaoying Chen, Hongrui Li, Wei Chen, Qianqian Di, Xunwei Li, Jiajing Zhao, Han Wu, Jin Chen, Yue Xiao, Zherui Wu, Weilin Chen RIG-I and STING are critical for mediating the RIG-I and cGAS-STING signaling pathways that guard against viral infection. Here, we report that ubiquitin-specific peptidase 39 (USP39) positively regulates the RIG-I and cGAS-STING pathways to induce antiviral innate immunity in vitro and in vivo. The USP39 deficiency impaired the antiviral immune response of macrophages, leading to low type I IFNs expression, and high RNA and (e.g., VSV, H1N1 PR8) DNA virus (e.g., HSV-1) replication. Moreover, USP39-deficient mice were more sensitive to VS