Figure 1.

Overview of interferon signaling pathways in vertebrate hosts.

Production of interferons (IFNs) begins with the binding of viral molecules, such as genomic nucleic acids, to either cell surface or intracellular pattern recognition receptors (PRRs) [18,19]. The resulting signaling cascade activates transcription and secretion of IFNs, which then bind to their associated IFN receptor on the same and nearby cells. Binding of IFNs to their receptors activates a signal cascade by Janus tyrosine kinases (JAK) and tyrosine kinase (TYK) that leads to the phosphorylation of STAT1 and/or STAT2 [9,15]. For type I and III IFNs, STAT1 and STAT2 complex with IRF9 and bind to IFN-stimulated response elements (ISREs) to express IFN-stimulated genes (ISGs). For type II IFNs, phosphorylated STAT1 dimers bind to gamma-activated site (GAS) elements for ISG production [9,15]. In turn, ISGs mediate antiviral effects directly within infected cells, or further induce innate and adaptive immune responses [3,120]. Figure created using BioRender (https://biorender.com/). Abbreviation: ISG, IFN-stimulated gene.