Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Type I Interferons

  • Jerome A. LangerEmail author
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101827


Historical Background

Investigating the general phenomenon of “viral interference,” where the prior infection by one nonlethal virus might interfere with a subsequent infection of cells by a second virus, Isaacs, Lindenmann, and colleagues published a series of articles in 1957 showing that an inactivated influenza virus, reacting with cells of chick allantoic membrane, can elicit the secretion of a proteinaceous substance, “the interferon,” into the medium that can, when incubated with fresh cells, confer protection against viral infection on these cells (Isaacs and Lindenmann 1957). The next 20 years saw explorations of what types of cells could secrete “interferon,” what substances – viruses or chemical – could induce interferons and initial explorations of biological and therapeutic function. Heterogeneity of “interferon” was initially...

This is a preview of subscription content, log in to check access.


  1. Capobianchi MR, Uleri E, Caglioti C, Dolei A. Type I IFN family members: similarity, differences and interaction. Cytokine Growth Factor Rev. 2015;26:103–11.  https://doi.org/10.1016/j.cytogfr.2014.10.011. PMID: 25466633.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Casanova JL, Holland SM, Notarangelo LD. Inborn errors of human JAKs and STATs. Immunity. 2012;36:515–28.  https://doi.org/10.1016/j.immuni.2012.03.016. PMID: 22520845.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Crow MK, Olferiev M, Kirou KA. Targeting of Type I Interferon in Systemic Autoimmune Diseases. Transl Res. 2015;165:296–305.  https://doi.org/10.1016/j.trsl.2014.10.005. PMCID: PMC4306610.CrossRefPubMedPubMedCentralGoogle Scholar
  4. de Weerd NA, Samarajiwa SA, Hertzog PJ. Type I interferon receptors: biochemistry and biological functions. J Biol Chem. 2007;282:20053–7.  https://doi.org/10.1074/jbc.R700006200. PMID: 17502368.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Duncan CJA, Mohamad SMB, Young DF, Skelton AJ, Leahy TR, et al. Human IFNAR2 deficiency: Lessons for antiviral immunity. Sci Transl Med. 2015;30:307ra154.  https://doi.org/10.1126/scitranslmed.aac4227. PMCID: PMID: 26424569.CrossRefGoogle Scholar
  6. Fish EN, Platanias LC. Interferon receptor signaling in malignancy: A network of cellular pathways defining biological outcomes. Mol Cancer Res. 2014;12:1691–703.  https://doi.org/10.1158/1541-7786.MCR-14-0450. PMID: 25217450.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Forster SC, Tate MD, Hertzog PJ. MicroRNA as Type I Interferon-regulated transcripts and modulators of the innate immune response. Front Immunol. 2015;6:334.  https://doi.org/10.3389/fimmu.2015.00334. PMID: 26217335.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Hambleton S, Goodbourn S, Young DF, Dickinson P, Mohamad SM, et al. STAT2 deficiency and susceptibility to viral illness in humans. Proc Natl Acad Sci USA. 2013;110:3053–8.  https://doi.org/10.1073/pnas.1220098110. PMID: 23391734.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Honda K, Takaoka A, Taniguchi T. Type I interferon gene induction by the interferon regulatory factor family of transcription factors. Immunity. 2006;25:349–60.  https://doi.org/10.1016/j.immuni.2006.08.009. PMID: 16979567.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Honke N, Shaabani N, Zhang D-E, et al. Multiple functions of USP18. Cell Death and Disease. 2016;7;e2444.  https://doi.org/10.1038/cddis.2016.326. PMID: 27809302.CrossRefGoogle Scholar
  11. Isaacs A, Lindenmann J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957;147:258–67. Reprinted: J Immunol. 2015;195:1911-20. PMID: 26297790.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Ivashkiv LB, Donlin LT. Regulation of type I interferon responses. Nat Rev Immunol. 2014;14:36–49.  https://doi.org/10.1038/nri3581. PMID: 24362405.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Kotenko SV, Durbin, JE. Contribution of Type III interferons to antiviral immunity: Location, location, location. J Biol Chem. 2017 (epub ahead of publication)  https://doi.org/10.1074/jbc.R117.777102
  14. Langer JA, Cutrone EC, Kotenko S. The Class II cytokine receptor (CRF2) family: overview and patterns of receptor-ligand interactions. Cytokine Growth Factor Rev. 2004;15:33–48. PMID: 14746812.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Levy DE, Marié IJ, Durbin JE. Induction and function of type I and III interferon in response to viral infection. Curr Opin Virol. 2011;1:476–86.  https://doi.org/10.1016/j.coviro.2011.11.001. PMCID: PMC3272644.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Mostafavi S, Yoshida H, Devapregasan M, et al. Parsing the interferon transcriptional network and its disease associations. Cell. 2016;164:564–78.  https://doi.org/10.1016/j.cell.2015.12.032. PMID: 26824662.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Ng CT, Mendoza JL, Garcia KC, Oldstone MB. Alpha and beta type 1 interferon signaling: passage for diverse biologic outcomes. Cell. 2016;164:349–52.  https://doi.org/10.1016/j.cell.2015.12.027. PMID: 26824652.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Pestka S. The interferons: 50 years after their discovery, there is much more to learn. J Biol Chem. 2007;282:20047–51.  https://doi.org/10.1074/jbc.R700004200. PMID: 17502369.CrossRefPubMedPubMedCentralGoogle Scholar
  19. Reich NC. STATS get their move on. JAKSTAT. 2013;2:e27080.  https://doi.org/10.4161/jkst.27080. PMID: 24470978e27080.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Schneider WM, Chevillotte MD, Rice CM. Interferon-stimulated genes: A complex web of host defenses. Annu Rev Immunol. 2014;32:513–45.  https://doi.org/10.1146/annurev-immunol-032713-120231. PMID: 24555472.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Schreiber G, Piehler J. The molecular basis for functional plasticity in type I interferon signaling. Trends Immunol. 2015;36:139–49.  https://doi.org/10.1016/j.it.2015.01.002. PMID: 25687684.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Stark GR, Darnell Jr JE. The JAK-STAT pathway at twenty. Immunity. 2012;36:503–14.  https://doi.org/10.1016/j.immuni.2012.03.013. PMCID: PMC3909993.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PharmacologyRutgers-Robert Wood Johnson Medical SchoolPiscatawayUSA