cGAS–STING-mediated novel nonclassic antiviral activities

Abstract

Stimulatorof interferon genes (STING) is an intracellular sensor of cyclic dinucleotides involved in the innate immune response against pathogen- or self-derived DNA. For years, interferon (IFN) induction of cyclic GMP–AMP synthase (cGAS)–STING has been considered as a canonical pattern defending the host from viral invasion. The mechanism of the cGAS–STING–IFN pathway has been well-illustrated. However, other signalling cascades driven by cGAS–STING have emerged in recent years and some of them have been found to possess antiviral ability independent of IFN. Here, we summarize the current progress on cGAS–STING-mediated nonclassic antiviral activities with an emphasis on the nuclear factor-κB and autophagy pathways, which are the most-studied pathways. In addition, we briefly present the primordial function of the cGAS–STING pathway in primitive species to show the importance of IFN-unrelated antiviral activity from an evolutionary angle. Finally, we discuss open questions that need to be solved for further exploitation of this field.