Inhibition of dsDNA sensors by viruses

The STING pathway is an antimicrobial reaction that drives the type I IFN response. It is triggered by the unusual presence of DNA in the cytoplasm. This pathway is active against DNA viruses, but also against RNA viruses whose infection can induce the release of mitochondrial DNA into the host cytoplasm .


This process is oriented toward response to bacterial infection, but virus infection also trigger the innate immunity STING pathway and many viruses are counteracting its effects. Several receptors have been described to react to cytoplasmic DNA and activate Interferon response through STING activation: ZBP1 , DDX41 , IFI16 and cGAS .

IFI16 plays an essential antiviral role in nuclear viral DNA sensing. Herpesvirales do not expose their DNA in the cytoplasm, but still they induce IRF3-mediated antiviral response and this happens through IFI16.The way IFI16 distinguishes self nuclear DNA and foreign is under investigation, but the signaling seems to rely on IFI16 assembled in filaments on viral dsDNA.