DNA-PKcs is required for cGAS/STING-dependent viral DNA sensing in human cells

Abstract

To mount an efficient interferon response to virus infection, intracellular pattern recognition receptors (PRRs) sense viral nucleic acids and activate anti-viral gene transcription. The mechanisms by which intracellular DNA and DNA viruses are sensed are relevant not only to antiviral innate immunity, but also to autoinflammation and anti-tumour immunity through initiation of sterile inflammation by self-DNA recognition. The PRRs that directly sense and respond to viral or damaged self-DNA function by signalling to activate interferon regulatory factor (IRF)-dependent type one interferon (IFN-I) transcription. We and others have previously defined DNA-dependent protein kinase (DNA-PK) as an essential component of the DNA-dependent antiviral innate immune system. Here, we show that DNA-PK is essential for STING-dependent IFN-I responses in human cells during stimulation with exogenous DNA and infection with DNA viruses.