Signal transduction in the type I interferon system and viral countermeasures

Type I interferons (IFN) including IFNα/β are cytokines of the immune system with critical functions in innate and adaptive immune response. Secreted IFN acts via JAK/STAT signaling pathways to direct a huge gene expression program, including antiviral, apoptotic, survival and immune genes. Only recently, the molecular patterns and their receptors as well as the connected signaling pathways leading to transcriptional activation of IFN genes have been elucidated. Ubiquitous cytosolic RNA helicases like RIG-I which sense intracellular triphosphate RNAs and activate the IFN-controlling transcription factors IRF3 and IRF7 seem to play a major role in antiviral defense and immunity. Recognition of extracellular nucleic acids by a subset of Toll-like receptors in addition contributes to a generalized host IFN response. During co-evolution with the host, viruses have learned to counteract every piece of the IFN network. Learning from viruses how to target the IFN system may lead us to novel strategies for therapeutic intervention.