DNA viruses are a source of great morbidity and mortality throughout the world by causing many diseases; thus, we need substantial knowledge regarding viral pathogenesis and the host’s antiviral immune responses to devise better preventive and therapeutic strategies. The innate immune system utilizes numerous germ-line encoded receptors called pattern-recognition receptors (PRRs) to detect various pathogen-associated molecular patterns (PAMPs) such as viral nucleic acids, ultimately resulting in antiviral immune responses in the form of proinflammatory cytokines and type I interferons. The immune-stimulatory role of DNA is known for a long time; however, DNA sensing ability of the innate immune system was unraveled only recently. At present, multiple DNA sensors have been proposed, and most of them use STING as a key adaptor protein to exert antiviral immune responses. In this review, we aim to provide molecular and structural underpinnings on endosomal DNA sensor Toll-like receptor 9 (TLR9) and multiple cytosolic DNA sensors including cyclic GMP-AMP synthase (cGAS), interferon-gamma inducible 16 (IFI16), absent in melanoma 2 (AIM2), and DNA-dependent activator of IRFs (DAI) to provide new insights on their signaling mechanisms and physiological relevance. We have also addressed less well-understood DNA sensors such as DEAD-box helicase DDX41, RNA polymerase III (RNA pol III), DNA-dependent protein kinase (DNA-PK), and meiotic recombination 11 homolog A (MRE11). By comprehensive understanding of molecular and structural aspects of DNA-sensing antiviral innate immune signaling pathways, potential new targets for viral and autoimmune diseases can be identified.

DNA病毒通过引起许多疾病而成为全世界发病率高和致死率高的来源。因此，我们需要有关病毒发病机制和宿主抗病毒免疫反应的大量知识，以制定更好的预防和治疗策略。先天免疫系统利用多种称为模式识别受体（PRR）的种系编码受体来检测各种病原体相关分子模式（PAMP），例如病毒核酸，最终导致促炎性细胞因子和类型的抗病毒免疫反应我干扰素。DNA的免疫刺激作用已为人所知。但是，先天免疫系统对DNA的感知能力直到最近才被阐明。目前，已经提出了多种DNA传感器，并且大多数使用STING作为关键衔接蛋白来发挥抗病毒免疫反应。在这篇综述中，我们旨在提供内体DNA传感器Toll样受体9（TLR9）和多种胞质DNA传感器的分子和结构基础，包括环状GMP-AMP合酶（cGAS），干扰素-γ诱导型16（IFI16），黑色素瘤2（AIM2）和IRF的DNA依赖性激活剂（DAI），以提供有关其信号传导机制和生理相关性的新见解。我们还解决了人们不太了解的DNA传感器，例如DEAD-box解旋酶DDX41，RNA聚合酶III（RNA pol III），DNA依赖性蛋白激酶（DNA-PK）和减数分裂重组11同源物A（MRE11）。通过全面了解DNA感应抗病毒先天免疫信号通路的分子和结构方面，