Fig. 1: The receptors and downstream signaling pathways of type I, type II, and type III interferons (IFNs).
From: Type I and III interferon responses in SARS-CoV-2 infection
Type I and type III IFNs bind to the heterodimeric receptor complexes IFNAR1/IFNAR2 and IFNLR1/IL-10Rβ, respectively. Upon IFN binding, the receptor-associated kinases JAK1 and TYK2 phosphorylate STAT1 and STAT2. Together with IRF9, phosphorylated STAT1 and STAT2 form a trimeric complex called IFN-stimulated gene factor 3 (ISGF3). ISGF3 subsequently enters the nucleus and binds IFN-stimulated response elements (ISREs) to promote the transcription of hundreds of IFN-stimulated genes (ISGs). Type II IFN binds to the receptor complex composed of IFNGR1 and IFNGR2 and promotes the phosphorylation of STAT1 via JAK1 and JAK2. Phosphorylated STAT1 forms homodimers, which bind gamma-activated sequences (GASs) in the nucleus and induce proinflammatory gene expression. Unlike type III IFNs, type I IFNs can also signal via STAT1 homodimers and promote proinflammatory gene expression.
