Sensing DNA in Antiviral Innate Immunity

The innate immune system is crucial to defend against viruses or other pathogenic microbes in early phases of infection. The response starts with the detection of evolutionarily conserved structures, termed pathogen-associated molecular patterns (PAMPs), by a set of germline-encoded pattern-recognition receptors (PRRs). In the case of DNA virus or retrovirus infection, endosome-associated viral nucleic acids are recognized by toll-like receptor 9 (TLR9). Conversely, cytosolic viral DNA or reverse transcription intermediates (RTI) is detected by DNA sensors such as cyclic GMP-AMP synthase (cGAS), interferon gamma inducible protein 16 (IFI16), and other cytosolic DNA binding proteins. Following the detection of specific viral PAMPs, PRRs trigger the activation of intracellular signaling cascades, ultimately leading to the induction of type I interferons (IFNs), pro-inflammatory cytokines and antiviral genes through the activation of interferon regulatory factor 3 (IRF3) and IRF7. To ensure successful antiviral defenses and to avoid aberrant or dysregulation of host immune signaling, antiviral pathways need to be tightly regulated. We believe that the Research Topic will give updated insights into the dynamic fields of DNA sensing during innate antiviral immunity, and hope it will serve the purpose to encourage new researches.


This Research Topic will provide an overall picture of DNA sensing signal pathways. We welcome the submission of Original Research, Review, Mini-Review, Hypothesis and Theory, and Perspective articles that cover, but are not limited to, the following topics:

1. Mechanisms of different PRRs and their downstream key adaptors to trigger early antiviral innate immunity;
2. Mechanisms used by host cells to positively or negatively regulate DNA sensing signal pathway;
3. Viral immune evasion mechanisms by targeting immune sensors, adaptor molecules, intracellular kinases and transcription factors;

Keywords: DNA Sensing, Antiviral Innate Immunity, Pattern Recognition Receptors, Pathogen-Associated Molecular Patterns, cGAS, TLR9, type I IFNs