Innate immune responses to DNA viruses

The innate immune system acts as the first line of defense against pathogens, which is also essential for initiation of adaptive immunity. Innate immune responses are initiated by pattern-recognition receptors (PRRs), which recognize conserved molecular structures of pathogens called pathogen-associated molecular patterns (PAMPs). The infection of virus triggers a series of signaling events leading to transcriptional induction of type I interferons (IFNs) and proinflammatory cytokines. In recent years, the mechanisms of viral RNA recognition and RNA virus-triggered signaling pathways have been well studied. However, it remains unclear on how DNA virus infection is sensed by host cells and triggers the host antiviral defense. Although ten potential viral DNA sensors have been reported, none of them is validated as a generally used sensor for distinct DNA viruses in divergent cell types and animals. Here, we provide a summary and perspective on recent advances in innate immune responses to DNA viruses.