Interferons

Abstract

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.
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References

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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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How to Cite close
Ahmed, Chulbul M, and Johnson, Howard M(May 2017) Interferons. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000931.pub3]