Skip to main content
SpringerLink
Log in

The biology of interferon actions

  • Leading Article
  • Published:
Blut Aims and scope Submit manuscript

Summary

The interferons comprise a group of proteins which were first identified by their ability to protect cells against virus infections. They are synthesized and secreted by a variety of cell types in response to various inducers and exert their effects in vivo by interaction with specific cellular receptors. In this sense the interferons are analogous to polypeptide hormones. In recent years it has become clear that the interferons are capable of influencing cellular physiology and behavior in a number of ways. Their effects include antiviral actions, inhibition of cell growth and proliferation, regulation of the expression of specific genes, modulation of cell differentiation and activation of various cell types in the immune system. This review aims to summarize the current state of biology of interferon actions with special emphasis on the hemopoetic system.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Aguet M, Mogensen KE (1983) Interferon receptors. In: Gresser I (ed) Interferon, vol 5. Academic Press, London, pp 1–22

    Google Scholar 

  2. Aguet M, Gresser I, Hovanessian AG, Bandu MT, Blanchard B, Blangy D (1981) Specific high affinity binding of 125 J-labeled mouse interferon to a specific cell surface receptor. II. Analysis of binding properties. Virology 114: 585–588

    Google Scholar 

  3. Aguet M, Blanchard B (1981) High affinity binding of 125 I-labeled mouse interferon to a specific cell surface receptor. II. Analysis of binding properties. Virology 115: 249–261

    Google Scholar 

  4. Aune TM, Pierce CW (1982) Activation of a suppressor T-cell pathway by IFN. Proc Natl Acad Sci USA 79: 3808–3812

    Google Scholar 

  5. Baglioni C, Nilsen TW (1983) Mechanisms of antiviral actions of interferon. In: Gresser I (ed) Interferon, vol 5. Academic Press, London, pp 23–42

    Google Scholar 

  6. Beutler B, Cerami A (1986) Cachectin and tumor necrosis factor as two sides of the same biological coin. Nature 320: 584–587

    Google Scholar 

  7. Billard C, Sigaux F, Ferbus D, Castaigne S, Flandrin G, Degos L, Falcoff E, Aguet M (1987) Absence of interferon-receptors on hairy cells from a patient resistant to interferon-therapy. Cancer J 1: 231–232

    Google Scholar 

  8. Billard C, Sigaux F, Castaigne S, Valensi F, Flandrin G, Degos L, Falcoff E, Aguet M (1986) Treatment of hairy cell leukemia with recombinant alpha interferon: II. In vivo down-regulation of alpha interferon receptors on tumor cells. Blood 67: 821–826

    Google Scholar 

  9. Bishop JM (1982) Oncogenes. Sci Am 246: 80–82

    Google Scholar 

  10. Branca AA, Baglioni C (1982) Down regulation of the interferon receptor. J Biol Chem 257: 13197–13200

    Google Scholar 

  11. Cantrell DA, Smith KA: Transient expression of IL-2 receptors: consequences for T cell growth. J Exp Med 158: 1985–1990

  12. Carrel S, Schmidt-Kessen A, Giuffre L (1985) Recombinant interferon-gamma can induce the expression of HLA-DR and DC on DR-negative melanome cells and enhance the expression of HLA-ABC and tumor associated antigens. Eur J Immunol 15: 118–123

    Google Scholar 

  13. Chany C (1984) Interferon receptors and interferon binding. In: Friedman MR (ed) Interferon, vol 3. Elsevier Science Publishers BV, p 11–32

  14. Clemens M (1986) Interferons and oncogenes. Nature 313: 531–532

    Google Scholar 

  15. Clemens MJ, Mc Nurlan M (1985) Regulation of cell proliferation and differentiation by interferons. Biochem J 226: 345–360

    Google Scholar 

  16. Content J, Coutie P, Vanhecke A, Van Damme J, Cayphas S, Poupart P, De Wit L, Fiers W (1987) B cell growth modulating and differentiation activity of recombinant human 26-KD protein (BSF-2, HuIFN-Beta-2, HPFG) and preliminary characterization of its cell surface receptor. J Interferon Res 6: 700 (abstract)

    Google Scholar 

  17. DeMaeyer E, DeMaeyer-Guignard J (1983) Delayed hypersensitivity to Newcastle disease virus in high and low interferon-producing mice. J Immunol 130: 2392–2398

    Google Scholar 

  18. Dinarello CA (1984) Interleukin-1. Rev Infect Dis 6: 51–78

    Google Scholar 

  19. Donahoe RM, Huang KH (1976) Interferon preparations enhance phagocytosis in vivo. Infect Immun 13: 1250–1257

    Google Scholar 

  20. Einat M, Resnitzky D, Kimchi A (1985) Inhibitory effects of interferon on the expression of genes regulated by platelet-derived growth factor. Proc Natl Acad Sci USA 82: 7608–7612

    Google Scholar 

  21. Einat M, Resnitzky D, Kimchi A (1985) Close link between reduction of c-myc expression by interferon and G0/G1 arrest. Nature 313: 597–600

    Google Scholar 

  22. Epstein CJ, McManus NH, Epstein LB, Branco AA, D'Alessandro SB, Baglioni C (1982) Direct evidence that the gene product of the human chromosome 21 locus, IRFC, is the interferon-receptor. Biochem Biophys Res Commun 107: 1060–1066

    Google Scholar 

  23. Faltynek CR, Baglioni C (1984) Interferon is a polypeptide hormone. Microbiol Sci 1: 81–90

    Google Scholar 

  24. Faltynek RC, Princler GL, Rossio JL, Ruscetti FW, Maluish AE, Abrams PG, Foon KA (1986) Relationship of the clinical response and binding of recombinant interferon alpha in patients with lymphoproliferative diseases. Blood 67: 1077–1082

    Google Scholar 

  25. Friedman RM (1977) Antiviral activity of interferons. Bacteriol Rev 41: 543–567

    Google Scholar 

  26. Friedman RL, Stark GR (1985) Alpha-interferon induced transcription of HLA and methallothionein genes containing homologous upstream sequences. Nature 314: 637–639

    Google Scholar 

  27. Giedlund MA, Örn H, Wigzell H, Senik A, Gresser I (1987) Enhanced NK cell activity in mice injected with interferon and interferon inducers. Nature 273: 759–763

    Google Scholar 

  28. Greiner JW, Hand PH, Noguchi P, Fisher PB, Pestka S, Schlom S (1984) Enhanced expression of surface tumor-associated antigens on human breast and colon tumor cells after recombinant human leukocyte alpha-interferon treatment. Cancer Res 44: 3208–3214

    Google Scholar 

  29. Gresser I, Bandu MT, Brouty-Boye D (1974) Interferon and cell division IX. Interferon-resistant L 1210 cells: characteristics and origin. J Natl Cancer Inst 52: 553–559

    Google Scholar 

  30. Grossberg Se, Taylor JL (1984) Interferon effects on cell differentiation. In: Friedman RM (ed) Inteferons, vol 13: Mechanisms of production and action. Elsevier Science Publishers BV 1984, pp 299–317

  31. Herberman RB (1986) Effects of biological response modifiers on effector cells with cytotoxic activity against tumors. Semin Oncol 13: 195–204

    Google Scholar 

  32. Howard M, Paul WE (1983) Regulation of B-cell growth and differentiation by soluble factors. Annu Rev Immunol 1: 307–321

    Google Scholar 

  33. Inglot AD (1983) The hormonal concept of interferon. Archives of Virology 76: 1–13

    Google Scholar 

  34. Isaacs A, Lindemann J (1957) Virus interference. I. The interferon. Proc R Soc Ser B 147: 258–267

    Google Scholar 

  35. Jonak GJ, Knight JE (1984) Selective reduction of c-myc RNA in Daudi cells by human beta interferon. Proc Natl Acad Sci USA 81: 1747–1750

    Google Scholar 

  36. Kerr IM (1987) The 2–5 A system. A personal view. J Interferon Res 7: 505–510

    Google Scholar 

  37. Kirchner H (1984) Interferons, a group of multiple lymphokines. Springer Semin Immunopathol 7: 347–373

    Google Scholar 

  38. Kohase M, Henrikson-Destefano D, May LT, Vilcek J, Sehat PB (1986) Induction of beta-2 interferon by tumor necrosis factor: A homeostatic mechanism in the control of cell proliferation. Cell 45: 659–666

    Google Scholar 

  39. Kohase M, May LT, Tamm I, Vileck J, Sehgal PB (1986) A cytokine network in human diploid fibroblasts: Interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor and interleukin-1. Mol Cell Biol 7: 273–280

    Google Scholar 

  40. Lengyel P (1982) Biochemistry of interferons and their actions. Annu Rev Biochem 51: 251–282

    Google Scholar 

  41. Lengyel P (1987) Double-stranded RNA and interferon action. J Interferon Res 7: 511–519

    Google Scholar 

  42. Lindahl P, Leary P, Gresser I (1972) Enhancement by interferon of the specific cytotoxicity of sensitized lymphocytes. Proc Natl Acad Sci USA 60: 721–726

    Google Scholar 

  43. Lindahl-Magnusson P, Leary P, Gresser I (1972) Interferon inhibits DNA synthesis induced in mouse lymphocyte suspensions by phytohaemagglutinin or by allogeneic cells. Nature 237: 120–124

    Google Scholar 

  44. Marth Ch, Daxenbichler G, Mayer I, Gastl G, Huber C, Dapunt O (1987) Human interferon-gamma increases adhaesion of cultured carcinoma cell to the substratum. Cancer Lett 37: 59–69

    Google Scholar 

  45. Maxwell BL, Talpaz M, Gutterman JU (1985) Down-regulation of peripheral blood cell interferon receptors in chronic myelogenous leukemia patients undergoing human interferon (HuIFN) therapy. Int J Cancer 36: 23–28

    Google Scholar 

  46. Moore RN, Larsen HL, Horoshov PW, Rouse BT (1984) Endogenous regulation of macrophage proliferative expansion by colony stimulating factor-induced interferon. Science 223: 178–181

    Google Scholar 

  47. Moritz T, Kirchner H (1986) The effect of interferons on cellular differentiation. Blut 53: 361–370

    Google Scholar 

  48. Nathan CF, Murray HW, Wiebe ME, Rubin BY (1983) Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158: 670–685

    Google Scholar 

  49. Nilsen TW, Baglioni C (1979) Mechanism for discrimination between viral and host mRNA in interferon-treated cells. Proc Natl Acad Sci USA 76: 2600–2604

    Google Scholar 

  50. Nossal GJV (1987) The basic components of the immune system. N Engl J Med 316: 1320–1330

    Google Scholar 

  51. Paganelli KA, Evans SS, Ham T, Ozer H (1986) B cell growth factor-induced proliferation of hairy cell lymphocytes and inhibition by type I interferon in vitro. Blood 67: 937–942

    Google Scholar 

  52. Pauker K, Cantell K, Henle W (1962) Quantitative studies on viral interference in suspended L-cells: III. Effect of interfering viruses and interferon on the growth rate of cells. Virology 17: 324–334

    Google Scholar 

  53. Perussia B, Dayton ET, Fanning V, Thiagarajan P, Hoxie J, Trinchieri G (1983) Immune interferon and leukocyte-conditioned medium induce normal and leukemic myeloid cells to differentiate along the monocytic pathway. J Exp Med 158: 2058–2080

    Google Scholar 

  54. Pfeffer LM, Wang E, Tamm E, Tamm I (1980) Interferon effects on microfilament organization, cellular fibronectin distribution, and cell motility in human fibroblasts. J Cell Biol 85: 9–17

    Google Scholar 

  55. Rapp UR, Bonner TI, Moelling K, Bister K, Ihle J (1985) Genes and gene products involved in growth regulation of tumor cells. In: Haveman K and Sorensen G (eds) Recent Results in Cancer Research, vol 99, New York, pp 211–228

  56. Rapp U, Storm SM, Cleveland JL (1987) Oncogenes and interferon. J Interferon Res (in press)

  57. Rashidbaigi A, Langer JA, Jung V, Jones C, Morse HG, Tischfield JA, Trill JJ, Kung H, Pestka S (1986) The gene for the human immune interferon receptor is located on chromosome 6. Proc Natl Acad Sci USA 83: 384–388

    Google Scholar 

  58. Resnitzky D, Yarden A, Zipari D, Kimchi A (1986) Autocrine beta-related interferon controls c-myc suppression and growth arrest during hematopoietic cell differentiation. Cell 46: 31–40

    Google Scholar 

  59. Rozengurt E (1983) Growth factors, cell proliferation and cancer: an overview. Mol Biol Med 1: 169–181

    Google Scholar 

  60. Rubinstein MV (1984) Multiple interferon subtypes: the phenomenon and it relevance. J Interferon Res 7: 545–551

    Google Scholar 

  61. Samuel CE (1979) Mechanisms of interferon action: phosphorylation of protein synthesis initiation factor eIF-2 in interferon-treated cells by a ribosome-associated kinase possessing site specificity similar to hemin-regulated rabbit reticulocyte kinase. Proc Natl Acad Sci USA 76: 600–607

    Google Scholar 

  62. Schreiber RD, Pace JL, Russel SW, Altman A, Katz DH (1983) Macrophage-activating factor produced by a T cell hybridoma: physiocochemical and biosynthetic resemblance to gamma-interferon. J Immunol 131: 826–833

    Google Scholar 

  63. Seghal PB, May LT (1987) Human interferon-beta 2. J Interferon Res 7: 521–527

    Google Scholar 

  64. Sen GC (1984) Biochemical pathways in interferon-action. Pharmacol Ther 24: 235–257

    Google Scholar 

  65. Sen GC, Shaila S, Lebleu B, Brown GE, Desrosiers RC, Lengyel P (1977) Impairment of retrovirus mRNA methylation in extracts of interferon-treated Ehrlich ascites tumor cells: further characteristics of the phenomenon. J Virol 21: 69–83

    Google Scholar 

  66. Sen GC, Taira H, Lengyel P (1978) Interferon, double-stranded RNA and protein phosphorylation. J Biol Chem 253: 5915–5921

    Google Scholar 

  67. Shows TB, Sakaguchi AY, Naylor SL, Goeddel DV, Lawn RM (1982) Clusterings of leukocyte and fibroblast interferon clones on human chromosome 9. Science 218: 373–376

    Google Scholar 

  68. Stark GR, Friedman, Mc Mahon M, Manly S, Kelly JM, Kerr IM (1984) Induction of human mRNAs by interferon. Phil Trans R Soc Lond B 307: 227–230

    Google Scholar 

  69. Tovey MG, Rochette-Egly C (1980) The effect of interferon on cyclic nucleotides. Ann NY Acad Sci 350: 266–278

    Google Scholar 

  70. Treisman R (1985) Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell 42: 889–902

    Google Scholar 

  71. Trinchieri G, Perussia B (1985) Immune interferon: a pleiotropic lymphokine with multiple effects. Immunology Today 6: 131–136

    Google Scholar 

  72. Troppmair J, Auböck J, Niederwieser D, Schönitzer D, Huber Ch (1987) Interferons (IFNs) and tumor necrosis factors (TNFs) in T-cell mediated immune responses against alloantigens. I. Influence on the activation of resting and antigen-primed T cells. Immunobiology (in press)

  73. Varmus HE (1984) The molecular genetics of cellular oncogenes. Ann Rev Genet 18: 553–612

    Google Scholar 

  74. Wallach D, Fellous M, Revel M (1982) Preferential effect of gamma-interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature 299: 833–840

    Google Scholar 

  75. Weissenbach J, Chernajovski Y, Zeevi M, Shulam L, Soreq H, Nir V, Wallach D, Perricaudet M, Tiollais P, Revel M (1980) Two interferon mRNAs in human fibroblasts: In vitro translation and Escherichia coli studies. Proc Natl Acad Sci USA 77: 7152–7156

    Google Scholar 

  76. Welsh RM, Kärre K, Hanson M, Kunkel LA, Kisslinger RW (1981) Interferon-mediated protection of normal and tumor target cells against lysis by mouse natural killer cells. J Immunol 1: 219–224

    Google Scholar 

  77. Wong GHW, Goeddel DV (1986) Tumor necrosis factor alpha and beta inhibit virus replication and synergize with interferon. Nature 323: 819–822

    Google Scholar 

  78. Zinn K, Maniatis T (1986) Detection of factors that interact with the human beta-interferon regulatory region in vivo by DNAse I footprinting. Cell 45: 611–618

    Google Scholar 

  79. Zoon K, Arnheiter H (1984) Studies on the interferon receptors. Pharmacol Ther 24: 259–278

    Google Scholar 

  80. Zoon KC, Arnheiter H, Zur Nedden D, Fitzgerald DJP, Willingham MC (1983) Human interferon alpha enters cells by receptor-mediated endocytosis. Virology 130: 195–203

    Google Scholar 

  81. Zullo JN, Cochran BH, Huang AS, Stiles CD (1985) Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3 T 3 cells. Cell 43: 793–800

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Immunobiology, Department of Internal Medicine, University of Innsbruck, Anichstrasse 35, A-6020, Innsbruck, Austria

    Günther Gastl & Christoph Huber

Authors
  1. Günther Gastl
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christoph Huber
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This work was financially supported by the Austrian Research Fund “Zur Förderung der wissenschaftlichen Forschung” and by the “Ernst Boehringer Institut für Arzneimittelforschung”, Vienna, Austria

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gastl, G., Huber, C. The biology of interferon actions. Blut 56, 193–199 (1988). https://doi.org/10.1007/BF00320105

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00320105

Key words

Search

Navigation