The Porcine Cyclic GMP-AMP Synthase-STING Pathway Exerts an Unusual Antiviral Function Independent of Interferon and Autophagy
Sen Jiang, Nengwen Xia, Jia Luo, Youwen Zhang, Qi Cao, Jiajia Zhang, Yuening Wang, Yuan Zhao, Wanglong Zheng, Nanhua Chen, François Meurens, Xiangdong Li, Jianzhong Zhu
Abstract
The IFN-independent antiviral function of the cGAS-STING pathway has attracted great attention in recent years; however, the nature of this IFN-independent antiviral function is unknown, although STING-induced autophagy has been shown to mediate the STING antiviral activity. First, we analyzed the antiviral activity through the porcine cGAS-pSTING pathway and established that pSTING signaling exerts an IFN-independent antiviral function. Second, we found that pSTING-induced IFN-independent autophagy and the antiviral activity of pSTING are independent of both IFN and autophagy. Finally, pSTING signaling activates cell apoptosis independently of IFN and autophagy, and the apoptosis is associated with antiviral activity. Our results suggest that pSTING-activated apoptosis at least partially mediates the antiviral activity or multiple pSTING-activated signals, including IFN production, nuclear factor κ light chain enhancer of activated B cells (NF-κB) expression, autophagy, and apoptosis, exert a redundant antiviral role. Thus, the work reveals a new layer of complexity in STING antiviral activity.