Abstract
Recent studies have shown that the human, mouse and bovine interferon (IFN) families consist of various gene products which may be both functionally and structurally heterogeneous. For example, the existence of multiple gene products of the IFN a family suggests that there may be specific roles for different molecular subtypes during stages of differentiation and development (Nagata et al., 1980). The capacity of interferon to exhibit such diverse activities is reflected by the multiplicity of biochemical responses detected in interferon-treated cells (Gordon and Minks, 1981; Borden and Ball, 1982; Lengyel, 1982). Most interferons share the same biochemical activities but quantitative differences are apparent among molecular subtypes as reflected by the differential activity on cells from different species. Although classically described as antiviral agents, the biochemical changes interferons elicit in cells are not selectively antiviral but sufficiently diverse to affect both viral and cellular metabolism. Nevertheless, the recent major advances in understanding the mechanism of action of interferon have come mainly from studies on the inhibition of viral replication.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Aguet, M. 1980, High-affinity binding of 125 I-labelled mouse interferon to a specific cell surface receptor, Nature, 284:459.
Baglioni, C., Minks, M.A., and Maroney, P.A. 1978, Interferon action may be mediated by activation of a nuclease by pppA2′p5′A2′p5′A, Nature, 273:684.
Ball, L.A. 1979, Induction of 2′5′-oligoadenylate synthetase activity and a new protein by chick interferon, Virology, 94:282.
Ball, L.A. 1980, Induction, purification, and properties of 2′5′ oligoadenylate synthetase, Ann. N.Y. Acad. Sci., 350:486.
Ball, L.A., and White, C.N. 1978, Oligonucleotide inhibitor of protein synthesis made in extracts of interferon-treated chick embryo cells: comparison with the mouse low molecular weight inhibitor, Proc. Natl. Acad. Sci. USA, 75:1167.
Ball, L.A., and White, C.N. 1979, Induction, purification, and properties of 2′5′-oligoadenylate synthetase, in: “Regulation of Macromolecular Synthesis”, G. Koch and D. Richter, eds., Academic Press, New York, pp. 303–317.
Beck, G., Poindron, P., Illinger, D., Beck, J.P., Ebel, J.P., and Falcoff, R. 1974, Inhibition of steroid inducible tyrosine aminotransferase by mouse and rat interferon in hepatoma tissue culture cells, FEBS Lett., 48:297.
Borden, E.C., and Ball, L.A. 1982, Interferons: biochemical cell growth inhibitory, and immunological effects, Prog. Hematol., 12:299.
Branca, A.A., and Baglioni, C. 1981, Evidence that types I and II interferons have different receptors, Nature, 294:768.
Branca, A.A., and Baglioni, C. 1982, Human interferon: binding to and degradation by a human cell line, J. Cell. Biochem. (suppl.), 6:95.
Cayley, P.J., Knight, M., and Kerr, I.M. 1982, Virus-mediated inhibition of the ppp(A2’p) A system and its prevention by interferon, Biochem. Biophys. Res. Commun., 104:376.
Clemens, M.J., Pain, V.M., Wong, S.T., and Henshaw, E.C. 1982, Phosphorylation inhibits guanine nucleotide exhange on eukaryotic initiation factor 2, Nature, 296:93.
Clemens, M.J., and Williams, B.R.G. 1978, Inhibition of cell-free protein synthesis by pppA2′ p5′ A 2′ p5′ A: a novel oligonucleotide synthesized by interferon-treated L cell extracts, Cell, 13:565.
Doetsch, P., Wu, J.M., Sawada, Y., and Suhadolnik, R.J. 1981, Synthesis and characterization of (2′-5′)ppp3′dA(p3′dA)n, an analogue of (2′-5′)pppA8pA), Nature, 291:355.
Dougherty, J.P., Samantha, H., Farrell, P.J., and Lengyel, P. 1980, Interferon, double-stranded RNA, and RNA degradation: isolation of homogeneous pppA(2′p5′A)n-1. synthetase from Ehrlich ascites tumor cells, J. Biol. Chem. 255:3813.
Epstein, D.A., Czarniechki, C.W., Jacobsen, H., Friedman, R.M., and Panet, A. 1981, A mouse cell line, which is unprotected by interferon against lytic virus infection, lacks ribonuclease F activity, Eur. J. Biochem., 118:9.
Epstein, D.A., Torrence, P.F., and Friedman, R.M. 1980, Double-stranded RNA inhibits a phosphoprotein phosphatase present in interferon-treated cells, Proc. Natl. Acad. Sci. USA, 77:107.
Farrell, P.J., Balkow, K., Hunt, T., Jackson, R.J., and Trachsel, H. 1977, Phosphorylation of initiation factor eIF-2 and the control of reticulocyte protein synthesis, Cell, 11:187.
Fellous, M., Nir, U., Wallach, D., Merlin, G., Rubinstein, M., and Revel, M. 1982, Interferon-dependent induction of mRNA for the major histocompatibility antigens in human fibroblasts and lymphoblastoid cells, Proc. Natl. Acad. Sci. USA, 79:3082.
Fitzpatrick, F.A., and Stringfellow, D.A. 1980, Virus and interferon effects on cellular prostaglandin biosynthesis, J. Immunol., 125:431.
Fuse, A., and Kuwata, T. 1978, Inhibition of DNA synthesis and alteration of cyclic adenosine 3′, 5′-monophosphate levels in RSa cells by human leukocyte interferon, J. Natl. Cancer Inst., 60:1227.
Gewart, D.R., Shah, S., and Clemens, M.J. 1981, Inhibition of cell division by interferons: changes in the transport and intracellular metabolism of thymidine in human lymphoblastoid (Daudi) cells. Eur. J. Biochem., 116:487.
Golgher, R.R., Williams, B.R.G., Gilbert, C.S., Brown, R.E., and Kerr, I.M. 1980, Protein kinase activity and the natural occurrence of 2–5A in interferon-treated EMC virus-infected L-cells, Ann. N.Y. Acad. Sei., 350:448.
Gordon, J., and Minks, M.A. 1981, The interferon-renaissance: molecular aspects of induction and action, Microbiol. Rev., 45:244.
Gupta, S.L. 1979, Specific protein phosphorylation in interferon-treated uninfected and virus-infected mouse L929 cells: enhancements by double-stranded RNA, J. Virol., 29:301.
Gupta, S.L., Rubin, B.Y., and Holmes, S.L. 1981, Regulation of interferon action in human fibroblasts: transient induction of specific proteins and amplification of the antiviral response by actinomycin D, Virology, 111:331.
Holmes, S.L., and Gupta, S.L. 1982, Interferon action in human fibroblasts: induction of 2′5′-oligoadenylate synthetase in the absence of detectable protein kinase activity, Arch. Virol., 72:137.
Hovanessian, A.G., Brown, R.E., and Kerr, I.M. 1977, Synthesis of a low molecular weight inhibitor of protein synthesis with enzyme from interferon-treated cells, Nature, 268–537.
Hovanessian, A.G., Menes, E., and Montagnier, L. 1981, Lack of systematic correlation between the interferon mediated antiviral state and the levels of 2-5A synthetase and protein kinase in three different types of murine cells, J. Interferon Res., 1:179.
Hovanessian, A.G., and Riviere, Y. 1980, Interferon-mediated induction of 2-5A synthetase and protein kinase in the liver and spleen of mice infected with Newcastle disease virus or injected with poly(I) poly(C), Ann. Virol., 131E:501.
Hovanessian, A.G., Riviere, Y., Montagnier, L., Michelson, M., Lacour, J., and Lacour, F. 1982, Enhancement of interferon-mediated protein kinase in mouse and human plasma in response to treatment with polyadenylic-polyuridylic acid (Poly A:Poly U), J. Interferon Res., 2:209.
Hovanessian, A.G., Wood, J., Meurs, E., and Montagnier, L. 1979, Increased nuclease activity in cells treated with pppA2′p5′A2′p5′A, Proc. Natl. Acad. Sci. USA, 76:3261.
Illinger, D., Coupin, G., Richards, M., and Poindron, P. 1976, Rat interferon inhibits steroid-inducible glycerol 3-phosphate dehydrogenase synthesis in a rat glial cell line, FEBS Lett., 64:391.
Justesen, J., Ferbus, D., and Thang, M.N. 1980a, Elongation mechanism and substrate specificity of 2′, 5′-oligoadenylate synthetase, Proc. Natl. Acad. Sci. USA., 77:4618.
Justesen, J., Ferbus, D., and Thang, M.N. 1980b, 2′5′ oligoadenylate synthetase, an interferon induced enzyme: direct assay methods for the products, 2′5′ oligoadenylates and 2′5′ co-oligonucleotides, Nucleic Acids Res., 8:3073.
Kerr, I.M., and Brown, R.E., 1978, pppA2′p5′A2′p5A: an inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells, Proc. Natl. Acad. Sci. USA, 75:256.
Kerr, I.M., Brown, R.E., and Ball, L.A. 1974, Increased sensitivity of cell-free protein synthesis to double-stranded RNA after interferon treatment, Nature, 250:57.
Kimchi, A., Shulman, L., Schmidt, A., Chernajovsky, Y., Fradin, A., and Revel, M. 1979, Kinetics of the induction of three translation-regulatory enzymes by interferon, Proc. Natl. Acad. Sci. USA, 76:3208.
Kimchi, A., Shure, H., and Revel, M. 1981, Anti-mitogenic function of interferon-induced (2′-5′) oligo(adenylate) and growth-related variations in enzymes that synthesize and degrade this oligonucleotide, Eur. J. Biochem., 114:5.
Knight, M., Cayley, P.J., Silverman, R.H., Wreschner, D.H., Gilbert, C.S., Brown, R.E., and Kerr, I.M. 1980, Radioimmune, radiobinding and HPLC analysis of 2-5A and related oligonucleotides from intact cells, Nature, 288:189.
Krishnamurti, C., Besancon, F., Justesen, J., Poulsen, K., and Ankel, H. 1982, Inhibition of mouse fibroblast interferon by gangliosides. Differential effects on biological activity and on induction of (2′-5′) oligoadenylate synthetase, Eur. J. Biochem., 124:1.
Krishnan, I., and Baglioni, C. 1980a, Increased levels of (2′-5′) oligo(A) polymerase activity in human lymphoblastoid cells treated with glucocorticoids, Proc. Natl. Acad. Sci. USA, 77:6506.
Krishnan, I., and Baglioni, C. 1980b, 2′5′ oligo(A) polymerase activity in serum of mice infected with EMC virus or treated with interferon, Nature, 285:485.
Lebleu, B., Sen, G.C., Shaila, S., Cabrer, B., and Lengyel, P. 1976, Interferon, double-stranded RNA, and protein phosphorylation, Proc. Natl. Acad. Sci. USA, 73:3107.
Lengyel, P. 1982, Biochemistry of interferons and their actions, Annu. Rev. Biochem., 51:251.
Lengyel, P., Samanta, H., Dougherty, J.P., Brawner, M.E., and Schmidt, H. 1982, Interferons and gene activation: cloning of cDNA segments complementary to messenger RNA’s induced by interferons, J. Cell Biochem. (suppl.), 6:81.
Levin, D.H., Petryshyn, R., and London, I.M. 1980, Characterization of double-stranded-RNA-activated kinase that phosphorylates a subunit of eukaryotic initiation factor 2(eIF-2α) in reticulocyte lysates, Proc. Natl. Acad. Sci. U.S.A., 77:832.
Lewis, J.A., Falcoff, E., and Falcoff, R. 1978, Dual action of double-stranded RNA in inhibiting protein synthesis in extracts of interferon-treated mouse L cells: translation is impaired at the level of initiation and by mRNA degradation, Eur. J. Biochem., 86:497.
Maheshwari, R.K., Banerjee, D.K., Waechter, C.J., Olden, K., and Friedman, R.M. 1980, Interferon treatment inhibits glycosylation of a viral protein, Nature, 287:454.
Mannering, G.J., Renton, K.W., el Azhary, R., and Deloria, L.B. 1980, Effects of interferon-inducing agents on hepatic cytochrome P-450 drug metabolizing systems, Ann. N.Y. Acad. Sei., 350:314.
Martin, E.M., Birdsall, N.J.M., Brown, R.E., and Kerr, I.M. 1979, Enzymic synthesis, characterisation and nuclear-magnetic-resonance spectra of pppA2′p5′A2′p5′A and related oligonucleotides: comparison with chemically synthesised material, Eur. J. Biochem., 95:295.
Matsuno, T., Shirasawa, N., and Kohno, S. 1976, Interferon suppresses glutamine synthetase induction in chick embryonic neural retina, Biochem. Biophys. Res. Commun., 70:310.
Meurs, E., Hovanessian, A.G., and Montagnier, L. 1981, Interferon mediated antiviral state in human MRCS cells in the absence of detectable levels of 2–5A synthetase and protein kinase, J. Interferon Res., 1:219.
Merritt, J.A., Borden, E.C., and Ball, L.A. 1982, Measurement of 2′5′ oligoadenylate synthetase in human mononuclear cells, J. Cell Biochem. (suppl.), 6:97.
Minks, M.A., Benvin, S., and Baglioni, C. 1980, Mechanism of pppA(2′p5′A)n 2′p5′AOH synthesis in extracts of interferon-treated HeLa cells, J. Biol. Chem., 255:5031.
Minks, M.A., West, D.K., Benvin, S., and Baglioni, C. 1979, Structural requirements of double-stranded RNA for the activation of 2′, 5′-oligo(A) polymerase and protein kinase of interferon-treated HeLa cells, J. Biol. Chem., 254:10180.
Nagata, S., Mantei, N., and Weissmann, C. 1980, The structure of one of the eight or more distinct chromosomal genes for human interferon-α, Nature, 287:401.
Nebert, D.W., and Friedman, R.M. 1973, Stimulation of aryl hydrocarbon hydroxylase induction in cell cultures by interferon, J. Virol., 11:193.
Nilsen, T.W., and Baglioni, C. 1979, Mechanism for discrimination between viral and host mRNA in interferon-treated cells, Proc. Natl. Acad. Sci. U.S.A., 76:2600.
Nilsen, T.W., Maroney, P.A., and Baglioni, C. 1981, Double-stranded RNA causes synthesis of 2′, 5′-oligo(A) and degradation of messenger RNA in interferon-treated cells, J. Biol. Chem., 256:7806.
Nilsen, T.W., Maroney, P.A., Robertson, H.D., and Baglioni, C. 1982, Heterogeneous nuclear RNA promotes synthesis of (2′, 5′) oliogadenylate and is cleaved by the (2′, 5′) oligoadenylate-activated endoribonuclease, Mol. Cell Biol., 2:154.
Nilsen, T.W., Wood, D.L., and Baglioni, C. 1980, Virus-specific effects of interferon in emnryonal carcinoma cells, Nature, 286:178.
Orchansky, P., Rubinstein, M., and Sela, I. 1982, Human interferons protect plants from virus infection, Proc. Natl. Acad. Sci. U.S.A., 79:2278.
Panet, A., Czarniecki, C.W., Falk, H., and Friedman, R.M. 1981, Effect of 2′5′-oligoadenylic acid on a mouse cell line partially resistant to interferon, Virology, 114:567.
Roberts, W.K., Hovanessian, A., Brown, R.E., Clemens, M.J., and Kerr, I.M. 1976, Interferon-mediated protein kinase and low-molecular-weight inhibitor of protein synthesis, Nature, 264–477.
Rochette-Egly, C., and Tovey, M.G. 1982, Interferon enhances guanylate cyclase activity in human lymphoma cells, Biochem. Biophys. Res. Commun., 107:150.
Samanta, H., Dougherty, J.P., and Lnegyel, P. 1980, Synthesis of (2′-5′)(A)n. from ATP: characteristics of the reaction catalyzed by (2′-5′)(A)n. synthetase purified from mouse Ehrlich ascites tumor cells treated with interferon, J. Biol. Chem., 255:9807.
Samuel, C.E. 1979, Mechanism of interferon action: phosphorylation of protein synthesis initiation factor eIF-2 in interferon-treated human cells by a ribosome-associated kinase processing site specificity similar to hemin-regulated rabbit reticulocyte kinase, Proc. Natl. Acad. Sci. U.S.A.., 76:600.
Schattner, A., Merlin, G., Wallach, D., Rosenberg, H., Bino, T., Hahn, T., Levin, S., and Revel, M. 1981, Monitoring of interferon therapy by assay of (2′-5′) oligo-isoadenylate synthetase in human peripheral white blood cells, J. Interferon Res., 1:587.
Schneck, J., Rager-Zisman, B., Rosen, O.M., and Bloom, B.R. 1982. Genetic analysis of the role of cAMP in mediating effects of interferon, Proc. Natl. Acad. Sci. U.S.A.., 79:1879.
Sekar, V., Atmar, V.J., Krim, M., and Kuehn, G.D. 1982, Interferon induction of polyamine-dependent protein kinase activity in Ehrlich ascites tumor cells, Biochem. Biophys. Res. Commun., 106:305.
Sen, G.C., Gupta, S.L., Brown, G.E., Lebleu, B., Rebello, M.A., and Lengyel, P. 1976, Interferon treatment of Ehrlich ascites tumor cells: effects on exogenous mRNA translation and tRNA inactivation in the cell extract, J. Virol., 17:191.
Sen, G.C., Shaila, S,, Lebleu, B., Brown, G.E., Desrosiers, R.C., and Lengyel, P. 1977, Impairment of reovirus mRNA methylation in extracts of interferon-treated Ehrlich ascites tumor cells: further characteristics of the phenomenon, J. Virol., 21:69.
Sen, G.C., Taira, H., and Lengyel, P. 1978, Interferon, double-stranded RNA, and protein phosphorylation: characteristics of a double-stranded RNA-activated protein kinase system partially purified from interferon-treated Ehrlich ascites tumor cells, J. Biol. Chem., 253:5915.
Shulman, L., and Revel, M. 1980, Interferon-dependent induction of mRNA activity for (2′5′)oligo-isoadenylate synthetase, Nature, 288:98.
Siegal, G.P., Thorgeirsson, U.P., Russo, R.G., Wallace, D.M., Liotta, L.A., and Berger, S.L. 1982, Interferon enhancement of the invasive capacity of Ewing sarcoma cells in vitro, Proc. Natl. Acad. Sci. U.S.A., 79:4064.
Siekierka, J., Mauser, L., and Ochoa, S. 1982, Mechanism of polypeptide chain initiation in eukaryotes and its control by phosphorylation of the a subunit of initiation factor 2, Proc. Natl. Acad. Sci. U.S.A., 79:2537.
Silverman, R.H., Cayley, P.J., Knight, M., Gilbert, C.S., and Kerr, I.M. 1982, Control of the ppp(A2fp)nA system in HeLa cells. Effects of interferon and virus infection, Eur. J. Biochem., 124:131.
Silverman, R.H., Wreschner, D.H., Gilbert, C.S., and Kerr, I.M. 1981, Synthesis, characterization and properties of ppp(A2fp) ApCp and related high-specific-activity P-labelled derivatives of ppp(A2fp) A, Eur. J. Biochem., 115:79.
Singh, G., Renton, K.W., and Stebbing, N. 1982, Homogeneous interferon from E. coli depresses hepatic cytochrome P-450 and drug biotransformation, Biochem. Biophys. Res. Commun., 106:1256.
Slattery, E., Ghosh, N., Samanta, H., and Lengyel, P. 1979, Interferon, double-stranded RNA, and RNA degradation: activation of an endonuclease by (2′-5′)An, Proc. Natl. Acad. Sci. U.S.A., 76:4778.
Sokawa, Y., Ando, T., and Ishihara, Y. 1980, Induction of 2′, 5′-oligoadenylate synthetase and interferon in mouse trigeminal ganglia infected with herpes simplex virus, Infect. Immunol., 28:719.
Sreevalsan, T., Rozengurt, E., Taylor-Papadimitriou, J., and Burchell, J. 1980, Differential effect of interferon on DNA synthesis: 2-deoxyglucose uptake and ornithine decarboxylase activity in 3T3 cells stimulated by polypeptide growth factors and tumor promoters, J. Cell Physiol., 104:1.
Stark, F.R., Dower, W.J., Schimke, R.T., Brown, R.E., and Kerr, I.M. 1979, 2–5A synthetase: assay, distribution and variation with growth or hormone status, Nature, 278–471.
Stewart, W.E., II, De Clercq, E., Billiau, A., Desmyter, J., and De Somer, P. 1972, Increased susceptibility of cells treated with interferon to the toxicity of polyriboinosinic acid. polyribocytidylic acid, Proc. Natl. Acad. Sci. U.S.A., 69:1851.
Williams, B.R.G., Golgher, R.R., Brown, R.E., Gilbert, C.S., and Kerr, I.M. 1979, Natural occurrence of 2–5A in interferon-treated EMC virus-infected L cells, Nature, 282:582.
Williams, B.R.G., Golgher, R.R., Hovanessian, A.G., and Kerr, I.M. 1980, The involvement of the 2–5A(pppA2′p5′A2′p5′A) system and protein kinases in the antiviral and anticellular effects of interferon, in: “Developments in Antiviral Therapy”, L.H. Collier and J. Oxford, eds., Academic Press, London, pp. 173–187.
Williams, B.R.G., and Kerr, I.M. 1978, Inhibition of protein
Williams, B.R.G., Kerr, I.M., Gilbert, C.S., White, C.N., and Ball, L.A. 1978, Synthesis and breakdown of pppA2′p5′A2′p5′A and transient inhibition of protien synthesis in extracts from interferon-treated and control cells, Eur. J. Biochem., 92:455.
Williams, B.R.G., and Read, S.E. 1981, Detection of elevated levels of interferon-induced 2-5A synthetase in infectious diseases and on parturition, in: “Proceedings of the Biology of the Interferon System”, E. De Maeyer, G. Galasso, and H. Schellekens, eds., Elsevier, New York, pp. 111–114.
Williams, B.R.G., Read, S.E., Freedman, M.H., Carver, D.H., and Gelfand, E.W. 1982, The assay of 2-5A synthetase as an indicator of interferonactivity and virus infection in vivo, in: “Chemistry and Biology of Interferons. Relationship to Therapeutics”, UCLA Symposia on Molecular and Cellular Biology XXV, T.C. Merigan, and R.M. Friedman, eds., Academic Press, New York.
Wood, J.N., and Hovanessian, A.G. 1979, Interferon enhances 2-5A synthetase in embryonal carcinoma cells, Nature, 282, 74.
Wreschner, D.H., McCauley, J.W., Skehel, J.J., and Kerr, I.M. 1981, Interferon action—sequence specificity of the ppp(A2′p)n-dependent ribonuclease, Nature, 289:414.
Wreschner, D.H., Silverman, R.H., James, T.C., Gilbert, CS., and Kerr, I.M. 1982, Affinity labelling and characterisation of the ppp(A2′p)nA-dependent endoribonuclease from different mammalian sources, Eur. J. Biochem., in press.
Yaron, M., Yaron, I., Gurari-Rotman, D., Revel, M., Lindner, H.R., and Zor, U. 1977, Stimulation of prostaglandin E production in culture human fibroblasts by poly(I) poly(C) and human interferon, Nature, 267:457.
Zilberstein, A., Kimchi, A., Schmidt, A., and Revel, M. 1978, Isolation of two interferon-induced translational inhibitors: a protein kinase and an oligo-isoadenylate synthetase, Proc. Natl. Acad. Sci. USA, 75:4734.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1983 Plenum Press, New York
About this chapter
Cite this chapter
Williams, B.R.G. (1983). Biochemical Actions. In: Sikora, K. (eds) Interferon and Cancer. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-1170-6_4
Download citation
DOI: https://doi.org/10.1007/978-1-4684-1170-6_4
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-1172-0
Online ISBN: 978-1-4684-1170-6
eBook Packages: Springer Book Archive