Interferons are a group of proteins defined primarily by their antiviral properties. There are three major types based on gene and protein structure, as well as receptors unique to the types. Type I interferons are composed of 15 or more members, type II of only one member and type III of four members. In addition to their defining antiviral activity, the interferons are multifunctional as immune regulators, cell function modulators and antitumor agents. Tyrosine kinases called Janus kinases (JAKs) and transcription factors called signal transducers and activators of transcription (STATs) are key players in gene activation by interferons, but the specificity of such activation is best understood in the context of ligand and receptor along with JAKs and STATs at the response elements of genes specifically activated by interferons.

Key Concepts

  • Interferons are a crucial group of proteins defined by their broad‐spectrum antiviral properties.
  • In addition to their antiviral properties, interferons play a key role in positive and negative immune regulation.
  • Type I interferon, β, negatively regulates the immune system and is thus a therapeutic for multiple sclerosis.
  • Type I interferon, α, exacerbates the autoimmune disease systemic lupus erythematosus.
  • The JAK/STAT signal transduction system plays a key role in gene activation by interferons.
  • The non‐canonical pathway of interferon signalling provides insight into the specificity of genetic and epigenetic aspects of interferon signalling.
  • The interferon system is a prototype for other cytokines, growth factors and hormones that use the JAK/STAT system.

Keywords: receptors; signal transduction; gene activation; antiviral; immunoregulation

Figure 1. Type I and type II IFN receptors and the molecules involved in signal transduction. Binding of the monomeric form of the type I IFN (a) and the asymmetrical heterodimer of IFNγ (b) to their respective receptors results in the activation of a tyrosine phosphorylation cascade involving the Janus kinases (Tyk2 and JAK2 for type I IFNs; JAK1 and JAK2 for IFNγ). Phosphorylation of the STAT transcription factors results in the formation of a heterodimer consisting of STAT 1 and STAT2 for the type I IFN or a homodimer of STAT1 for IFNγ.
Figure 2. Proposed model for ligand (IFNγ) binding to receptor and translocation of STAT transcription factors to the nucleus. Data demonstrate that binding of IFNγ via the C‐terminus to the cytoplasmic domain of the receptor (IFNγRα–cyto) enhances Janus kinase (JAK) binding. This, in turn, causes signal transducer and activator of transcription (STAT) binding. IFNγ provides the nuclear localisation sequence (NLS) for translocation to the nucleus; none of the other participants have been shown to possess an NLS. Data suggest that the β chain of the receptor does not undergo nuclear translocation. α, importin α; β, importin β; GAS, γ‐activated sequence; GTP, guanosine triphosphate.


Brehove M , Wang T , North J , et al. (2015 Histone core phosphorylation regulates DNA accessibility. Journal of Biological Chemistry 290 (37): 22612–22621. ISSN 1083‐351X. Disponível em: < .

Domanski P and Colamonici OR (1996) The type‐I interferon receptor: the long and short of it. Cytokine and Growth Factor Reviews 7: 143–151.

Egli A , Santer DM , O'Shea D , Tyrrell DL and Houghton M (2014 The impact of the interferon‐lambda family on the innate and adaptive immune response to viral infections. Emerging Microbes & Infections 3 (7): e51. Disponível em: <

Johnson HM , Subramaniam PS , Olsnes S and Jans DA (2004) Trafficking and signalling pathways of nuclear localizing protein ligands and their receptors. Bioassays 26: 993–1004.

Johnson HM and Ahmed CM (2016) Non‐canonical IFN signaling: mechanistic linkage of genetic and epigenetic events. Mediators of Inflammation 2016: 9.

Kotenko SV , Gallagher G , Baurin VV , et al. (2003 IFN‐lambdas mediate antiviral protection through a distinct class II cytokine receptor complex. Nature Immunology 4 (1): 69–77. ISSN 1529‐2908. Disponível em: <

McBride KM , Banninger G , McDonald C and Reich NC (2002) Regulated nuclear import of the STAT1 transcription factor by direct binding of importin‐alpha. EMBO Journal 21: 1754–1763.

Pestka S , Kotenko SV , Muthukumaran G , et al. (1997) The interferon gamma (IFN‐gamma) receptor: a paradigm for the multichain cytokine receptor. Cytokine and Growth Factor Reviews 8: 189–206.

Samuel CA (2001) Antiviral actions of interferons. Clinical Microbiology Reviews 14: 778–809.

Sheppard P , Kindsvogel W , Xu W , et al. (2003 IL‐28, IL‐29 and their class II cytokine receptor IL‐28R. Nature Immunology 4 (1): 63–68. ISSN 1529‐2908. Disponível em: <

Subramaniam PS , Torres BA and Johnson HM (2001) So many ligands, so few transcription factors: a new paradigm for signalling through the STAT transcription factors. Cytokine 15: 175–187.

Further Reading

Baron S and Dianzani F (1994) The interferons: a biological system with therapeutic potential in viral infections. Antiviral Research 24: 97–110.

Jans DA (1994) Nuclear signalling pathways for polypeptide ligands and their membrane receptors? FASEB Journal 8: 841–847.

Johnson HM , Bazer FW , Szente BE and Jarpe MA (1994) How interferons fight disease. Scientific American 270 (5): 68–75.

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Ahmed, Chulbul M, and Johnson, Howard M(May 2017) Interferons. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000931.pub3]