Fig. 1

Viral sensing pathways that trigger host immune responses. PRR signalling is triggered by viral proteins and nucleic acids (PAMPs) and host-derived DAMPs. All TLRs except TLR3 signal through the adapter molecule Myd88. TLR3 signals through TRIF, and TLR4 signals via both Myd88- and TRIF-dependant pathways. RIGI, MDA5 and NOD2 signal through the mitochondrial antiviral-signaling protein MAVS (or IPS1). These signalling pathways converge on IRF3/IRF7 and NFkB to activate their respective type I/III interferons and proinflammatory gene programs. Type I (IFN-α, IFN-β) and III interferons (IFN-λ1, IFN-λ2, IFN-λ3 or IL-29, IL-28A, IL-28B) bind to distinct receptor complexes, which activates STAT1 and STAT2 phosphorylation. IRF9 binds to STAT1/STAT2 heterodimers forming the ISGF3 complex, which translocates to the nucleus to induce transcription of ISGs that contain ISRE elements in their promoters. Type II interferon signalling activates STAT1, which translocates to the nucleus to induce transcription of ISGs containing GAS elements in their promoters. Some proinflammatory cytokines (pro-IL-1B, pro-IL-18) are produced in an inactive form. The processing of these cytokines into their bioactive form is mediated by Capase-1, which is activated by the NLRP3 inflammasome pathway