Fig. 1.

NHEJ and antiviral innate immunity. Damaged self-DNA and foreign viral DNA are both sensed by the DDR machinery (HR and NHEJ). The DDR machinery is responsible for repairing damaged DNA and ensuring survival of the cell. It also leads to the activation of a number of stress response pathways, which determine the fate of the cell, such as apoptosis/senescence, cellular antiviral state, etc. This graphic emphasizes the role of an NHEJ component, the DNA-PK complex, in antiviral immunity. DNA-PK recognizes intracellular viral DNA and activates the IFN innate immune response through activation of the STING adaptor protein or possibly via the direct phosphorylation of the IRF3 transcription factor. The indicated viral proteins suppress the innate immune response by blocking the signalling pathway at various stages. DDR, DNA damage response; HR, homologous recombination; NHEJ, non-homologous end-joining; DNA-PK, DNA-dependent protein kinase; STING, stimulator of IFN genes; IRF3, IFN regulatory factor 3; DNA-PKcs, DNA-dependent protein kinase catalytic subunit; HSV ICP0, herpes simplex virus infected cell polypeptide 0; VACV, vaccinia virus; AdV, adenovirus.