The interferon signaling pathway

The various IFNs function as extracellular cytokines that signal through specific dimeric cell surface receptors (IFNAR1/IFNAR2 for type I, IFNGR1/IFNGR2 for type II, IFNLR1/IL10RB for type III). Receptor engagement leads to activation of intracellular kinases (JAK1, JAK2, TYK2) that phosphorylase transcription factors STAT1 and STAT2. The activated transcription factors (ISGF3 or STAT1 homodimers) translocate to the nucleus to induce transcription of ISGs by binding ISRE or GAS promoter elements.

IFNA: interferon alpha; IFNB: interferon beta; IFNG: interferon gamma; IFNL: interferon lambda; IFNAR: interferon alpha receptor; IFNGR: interferon gamma receptor; IFNLR: interferon lambda receptor; IL10RB: interleukin 10 receptor beta; JAK: Janus kinase; TYK: tyrosine kinase; STAT: signal transducer and activator of transcription; IRF: interferon regulatory factor; DNA: deoxyribonucleic acid; ISRE: interferon-stimulated response element; GAS: gamma-activated sequence; ISGF: interferon-stimulated gene factor.

Adapted with permission of Annual Reviews, from: Schoggins JW. Interferon-stimulated genes: What do they all do? Annu Rev Virol 2019; 29:567; permission conveyed through Copyright Clearance Center, Inc. Copyright © 2019.

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The interferon signaling pathway