Functions of DNA damage machinery in the innate immune response to DNA virus infection

• Detection of DNA virus genomes is essential for host IFNI responses.
• DNA repair proteins are involved in sensing of intracellular foreign DNA.
• Cross-talk between DNA repair and innate immunity has implications for both systems.

DNA is potently immunostimulatory, and self-DNA is packaged in the nucleus or mitochondria allowing it to remain silent to cell-intrinsic sensors. However, damaged or mislocalised self-DNA is sensed by our innate immune systems, resulting in the production of type I interferons (IFNI), chemokines and inflammatory cytokines. During DNA virus infection the detection of viral DNA genomes by pattern recognition receptors (PRRs) is essential for the initiation of IFNI responses and host defence against these pathogens. It is intriguing that a number of molecular mechanisms have been found to be common to both of these DNA-induced stress responses and this has potentially important consequences for both sides of the host/pathogen arms race.