Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Department of Molecular Biology, Princeton University, Lewis Thomas Laboratory, Washington Road, Princeton, NJ 08544, USA.
Trends Microbiol. 2022 Nov;30(11):1056-1071. doi: 10.1016/j.tim.2022.05.004. Epub 2022 May 28.
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)-γ 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.
脊椎动物和哺乳动物宿主与 DNA 病毒的共同进化，促使宿主细胞在细胞核中区分病毒和细胞 DNA，从而诱导固有免疫反应。同时，病毒也产生了抑制 DNA 感应的机制。在这个病毒-宿主界面上，新出现的证据将细胞因子反应和细胞稳态途径联系起来，特别是 DNA 损伤反应 (DDR)。核 DNA 传感器，如干扰素 (IFN)-γ诱导蛋白 16 (IFI16)，与共济失调毛细血管扩张突变 (ATM)和 DNA 依赖性蛋白激酶 (DNA-PK) 的 DDR 调节剂在功能上相互作用。在这里，我们讨论 DDR-先天免疫信号轴的积累知识。通过这个感染驱动的信号轴的视角，我们展示了宿主和病毒分子策略的获得，以调节自身炎症和抗病毒反应。
