RNA viruses and the cGAS-STING pathway: reframing our understanding of innate immune sensing

The past decade has provided critical information about the cytoplasmic innate immune sensing pathway of cyclic GMPA-MP synthase (cGAS) and stimulator of interferon genes (STING). These discoveries have broadened our understanding of the interconnectedness of the cGAS-STING pathway with autophagy, programmed cell death, Rig-I-like receptor (RLR) signaling, DNA independent interferon induction, and how this pathway responds to RNA virus infection. These advances highlight how multiple families of RNA viruses are restricted by and in turn have mechanisms to inhibit cGAS-STING dependent type-I interferon (IFN-I) induction. Here we review recent discoveries of how and why the cGAS-STING pathway responds to infection with RNA viruses, novel findings of RNA viral antagonism of the cGAS-STING innate immune sensing pathway, and attempt to provide context for a shift in thinking as to how critical this DNA sensing pathway is for the restriction of a wide range of RNA viruses.

Automated summary

Recent research has provided critical information about the role of the cGAS-STING pathway in the immune response to RNA virus infection. This pathway is interconnected with autophagy, programmed cell death, RLR signaling, DNA independent interferon induction, and has mechanisms to restrict and be inhibited by RNA viruses.