How host cells recognize many kinds of RNA and DNA viruses and initiate innate antiviral responses against them has not yet been fully elucidated. Over the past decade, investigations into the mechanisms underlying these antiviral responses have focused extensively on immune surveillance sensors that recognize virus-derived components (such as lipids, sugars and nucleic acids). The findings of these studies have suggested that antiviral responses are mediated by cytosolic or intracellular compartment sensors and their adaptor molecules (e.g., TLR, myeloid differentiation primary response 88, retinoic acid inducible gene-I, IFN-β promoter stimulator-1, cyclic GMP-AMP synthase and stimulator of IFN genes axis) for the primary sensing of virus-derived nucleic acids, leading to production of type I IFNs, pro-inflammatory cytokines and chemokines by the host cells. Thus, host cells have evolved an elaborate host defense machinery to recognize and eliminate virus infections. In turn, to achieve sustained viral infection and induce pathogenesis, viruses have also evolved several counteracting strategies for achieving immune escape by targeting immune sensors, adaptor molecules, intracellular kinases and transcription factors. In this review, we discuss recent discoveries concerning the role of the cytosolic nucleic acid-sensing immune response in viral recognition and control of viral infection. In addition, we consider the regulatory machinery of the cytosolic nucleic acid-sensing immune response because these immune surveillance systems must be tightly regulated to prevent aberrant immune responses to self and non-self-nucleic acids. K E Y W O R D S cyclic GMP-AMP synthase, stimulator of IFN genes, interferon, viral immune evasionAbbreviations: AGS, Aicardi-Goutières syndrome; AIM2, absent in melanoma 2; AMFR, autocrine motility factor receptor; CDN, cyclic dinucleotide; cGAS, cyclic GMP-AMP synthase; cGAMP, cyclic GMP-AMP; DAI, DNA-dependent activator of IRF3; DENV, dengue virus; DNA-PKcs, DNAdependent protein kinase; dsDNA, double-stranded DNA; dsRNA, double-stranded RNA; DUB, de-ubiquitination; EIF3S5, eukaryotic translation initiation factor 3 subunit 5; ER, endoplasmic reticulum; HBV, hepatitis B virus; HCV, hepatitis C virus; HSV-1, herpes simplex virus-1; IAV, influenza A virus; IFI16, IFN-γ-inducible protein 16; IPS-1, IFN-β promoter stimulator-1; IRF3, interferon regulatory factor 3; iRhom2, inactive rhomboid protein 2; ISG, IFN-stimulated gene; JEV, Japanese encephalitis virus; KSHV, Kaposi sarcoma-associated herpesvirus; LANA, latency-associated nuclear antigen; MDA5, melanoma differentiation-associated protein 5; MHV68, murine gamma-herpesvirus 68; Mre11, meiotic recombination 11; NDV, Newcastle disease virus; NF-κB, nuclear factor-κB; NLR, NOD-like receptor; PPM1A, protein phosphatase, Mg2+/Mn2+ dependent 1A; PRR, pattern recognition receptor; PTM, post-translational modification; RIG-I, retinoic acid inducible gene-I; RNF5, RING finger protein 5; S6K1, S6 kinase 1; STING, stimulator of IFN genes; TBK1, T...

Host cells have evolved host defense machinery to restrict viral infection. However, viruses have evolved counteracting strategies to achieve their infection.