Nuclear antiviral innate responses at the intersection of DNA sensing and DNA repair

The coevolution of vertebrate and mammalian hosts with DNA viruses has driven the ability of host cells to distinguish viral from cellular DNA in the nucleus to induce intrinsic immune responses. Concomitant viral mechanisms have arisen to inhibit DNA sensing. At this virus-host interface, emerging evidence links cytokine responses and cellular homeostasis pathways, particularly the DNA damage response (DDR). Nuclear DNA sensors, such as the interferon (IFN)-gamma inducible protein 16 (IFI16), functionally intersect with the DDR regulators ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK). Here, we discuss accumulating knowledge for the DDR-innate immunity signaling axis. Through the lens of this infection-driven signaling axis, we present host and viral molecular strategies acquired to regulate autoinflammation and antiviral responses.

Automated summary

The coevolution of vertebrate and mammalian hosts with DNA viruses has led to the development of host cell abilities to differentiate viral and cellular DNA, triggering innate immune responses. This interaction has also resulted in viral mechanisms to inhibit DNA sensing. Within this virus-host interface, there is evidence linking cytokine responses and cellular homeostasis pathways, specifically the DNA damage response (DDR). Nuclear DNA sensors such as interferon (IFN)-gamma inducible protein 16 (IFI16) intersect with the DDR regulators ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK). In this article, we discuss the accumulating knowledge regarding the DDR-innate immunity signaling axis and present acquired host and viral molecular strategies to regulate autoinflammation and antiviral responses.