Abstract
The molecular mediators of interferon action are those cellular components which change in relative amount upon treatment with interferon. The mediators to be discussed in this chapter are enzymes which are synthesized at an increased rate in interferon-treated cells (Baglioni 1979). It should be pointed out that interferon induces the synthesis of several proteins in mammalian cells (Gupta et al. 1979; Knight and Korant 1979). These proteins can be identified as polypeptides with characteristic electrophoretic mobility by labeling the cells with radioactive amino acids and fractionating cell extracts by electrophoresis. The increase in these proteins is inhibited by actinomycin D, indicating that RNA synthesis is required for their induction by interferon (Farrell et al. 1980). The synthesis of these proteins begins a few hours after tissue culture cells are exposed to interferon, but is is transient, even in the continuous presence of this antiviral agent (Rubin and Gupta 1980). These proteins, however, have not been identified with specific enzymatic activities or cellular components and it is unclear at this time whether or how they are involved in the different activities of interferon.
Keywords
- Vesicular Stomatitis Virus
- Ehrlich Ascites Tumor Cell
- Molecular Mediator
- Antiviral Mechanism
- Interferon Action
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References
Baglioni C (1979) Interferon induced enzymatic activities and their role in the antiviral state. Cell 17:255–264
Baglioni C, Maroney PA (1981) Inhibition of double-stranded RNA activated protein kinase and 2′5′-oligo(A) polymerase by ethidium bromide. Biochemistry 20:758–765
Baglioni C, Minks MA, Maroney PA (1978) Interferon action may be mediated by activation of a nuclease by pppA2′p5′A2′p5′A. Nature 273:684–687
Baglioni C, Maroney PA, West DK (1979) 2′5′-oligo(A) polymerase activity and inhibition of viral RNA synthesis in interferon-treated HeLa cells. Biochemistry 18:1765–1770
Baglioni C, Minks MA, De Clercq E (1981 a) Structural requirements of polynucletides for the activation of (2′–5′)An polymerase and protein kinase. Nucleic Acids Res 19:4939–4950
Baglioni C, D’Alessandro SB, Nilsen TW, Den Hartog JA, Crea R, Van Boom JH (1981 b) Analogs of (2′–5′)oligo(A): Endonuclease activation and inhibition of protein synthesis in intact cells. J Biol Chem 256:3253–3257
Ball LA (1979) Induction of 2′II′oligoadenylate synthetase activity and a new protein by chick interferon. J Virol 94:282–296
Ball LA, White CN (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 75:1167–1171
Ball LA, White CN (1979) Induction, purification and properties of 2′5′-oligoadenylate synthetase. In: Koch G, Richter D (eds) Regulation of macromolecular synthesis by low molecular weight mediators. Academic, New York, pp 304–317
Banerjee AK (1980) 5′-Terminal cap structure in eukaryotic messenger ribonucleic acids. Microbiol Rev 44:175–205
Brown GE, Lebleu B, Kawakita M, Shaila S, Sen GC, Lengyel P (1976) Increased endonu-clease activity in an extract from mouse Ehrlich ascites tumor cells which had been treated with a partially purified interferon preparation: Dependence on double-stranded RNA. Biochem Bophys Res Commun 69:114–121
Chernajovsky Y, Kimchi A, Schmidt A, Zilberstein A, Revel M (1979) Differential effects of two interferon-induced translational inhibitors on initiation of protein synthesis. Eur J Biochem 96:35–41
Clemens MJ, Williams BRG (1978) Inhibition of cell-free protein synthesis by pppA2′-p5′A2′p5′A: a novel oligonucleotide synthesized by interferon-treated L cell extracts. Cell 13:565–572
De Ferra F, Baglioni C (1981 a) Viral messenger RNA unmethylated in the 5′-terminal guanosine in interferon-treated HeLa cells infected with vesicular stomatitis virus. Virology 112:426–435
De Ferra F, Baglioni C (1981 b) Changes in the level of the methyl donor S-adenosyl-methionine and its antagonist S-adenosylhomocysteine in HeLa cells treated with interferon. Abstr of the 2nd international congress for interferon research, San Francisco, Oct 1981
Desrosiers RC, Lengyel P (1977) Impairment of reovirus mRNA cap methylation in interferon-treated L cells. Fed Proc 36:812
Dougherty JP, Samantha H, Farrell PJ, Lengyel P (1980) Interferon, double-stranded RNA, and RNA degradation. J Biol Chem 255:3813–3816
Ehrenfeld E, Hunt T (1971) Double-stranded poliovirus RNA inhibits initiation of protein synthesis by reticulocyte lysates. Proc Natl Acad Sci USA 68:1075–1078
Epstein DA, Torrence PF, Friedman RM (1980) Double-stranded RNA inhibitis a phos-phoprotein phosphatase in interferon-treated cells. Proc Natl Acad Sci USA 77:107–111
Farrell PJ, Balkow K, Hunt T, Jackson R (1977) Phosphorylation of initiation factor eIF-2 and the control of reticulocyte protein synthesis. Cell 11:187–200
Farrell PJ, Sen GC, Dubois MF, Ratner L, Slattery E, Lengyel P (1978) Interferon action: Two distinct pathways for the inhibition of protein synthesis by double-stranded RNA. Proc Natl Acad Sci USA 75:5893–5897
Farrell PJ, Broeze RJ, Lengyel P (1980) Interferon induced mRNA and proteins in Ehrlich ascites tumor and HeLa cells. Ann NY Acad Sci 350:651–616
Field AK, Tytell AA, Lampson GP, Hilleman MR (1967) Inducers of interferon and host resistance. II. Multistranded synthetic polynucleotide complexes. Proc Natl Acad Sci USA 58:1004–1009
Floyd-Smith G, Slattery E, Lengyel P (1981) Interferon action: RNA cleavage pattern of a (2′–5′)oligoadenylate-dependent endonuclease. Science 212:1030–1032
Gupta SL, Rubin BY, Holmes SL (1979) Interferon action: Induction of specific proteins in mouse and human by homologous interferons. Proc Natl Acad Sci USA 76:4817–4821
Hovanessian AG, Brown RE, Kerr IM (1977) Synthesis of low molecular weight inhibitor of protein synthesis with enzyme from interferon-treated cells. Nature 268:537–540
Hovanessian AG, Kerr IM (1979) The (2′–5′)oligoadenylate (pppA2′–5′A2′5′A) synthetase and protein kinase(s) from interferon-treated cells. Eur J Biochem 93:515–526
Hovanessian AG, La Bonnardiere C, Falcoff E (1980) Action of murine γ (immune)-inter-feron on β (fibroblast)-interferon resistant L 1210 and embryonal carcinoma cells. J Interferon Res 1:125–136
Kaempfer R, Rosen H, Israeli R (1978) Translational control. Recognition of the methylated 5′-end and an internal sequence in eukaryotic mRNA by the initiation factor that binds methionyl-tRNAf met. Proc Natl Acad Sci USA 75:650–654
Kerr IM, Brown RE (1978) pppA2′p5′A2′p5′A: An inhibitor of protein synthesis synthe-sized with an enzyme fraction from interferon-treated cells. Proc Natl Acad Sci USA 75:256–260
Kerr IM, Brown RE, Ball LA (1974) Increased sensitivity of cell-free protein synthesis to double-stranded RNA after interferon-treatment. Nature 250:57–59
Kimchi A, Zilberstein A, Schmidt A, Shulman L, Revel M (1979) The interferon induced protein kinase PK-i from mouse L cells. J Biol Chem 254:9846–9853
Knight E Jr, Korant BD (1979) Fibroblast interferon induces synthesis of four proteins in human fibroblast cells. Proc Natl Acad Sci USA 76:1824–1827
Knight M, Cayley PJ, Silverman RH, Wreschner DH, Gilbert CS, Brown RE, Kerr IM (1980) Radioimmune, radiobinding and HPLC analysis of 2–5A and related oligonucleotides from intact cells. Nature 288:189–192
Krishnan I, Baglioni C (1980) Increased levels of (2′–5′)oligo(A) polymerase activity in human lymphoblastoid cells treated with glucocorticoids. Proc Natl Acad Sci USA 77:6506–6510
Krishnan I, Baglioni C (1981) Regulation of 2′5′-oligo(A) polymerase activity in quiescent human fibroblasts treated with interferon. Virology 111:666–670
Kroath H, Gross HJ, Jungwirth C, Bodo G (1978) RNA methylation in vaccinia virus-infected chick embryo fibroblasts treated with homologous interferon. Nucleic Acids Res 5:2441–2454
Lebleu B, Sen GC, Shaila S, Cabrer B, Lengyel P (1976) Interferon, doublestranded RNA and protein phosphorylation. Proc Natl Acad Sci USA 73:3107–3111
Lengyle P (1982) Biochemistry of interferons and their action. Ann Rev Biochem 51:251–282
Lengyel P, Desrosiers R, Broeze R, Slattery E, Taira H, Dougherty J, Samantha H, Pichon J, Farrell P, Ratner L, Sen G (1980) Biochemistry of the interferon system. In: Schlessinger D (ed) Microbiology. American Society of Microbiology, Bethesda, pp 219–226
Maheshwary RK, Friedman RM (1980) Effect of interferon treatment on vesicular stomatitis virus (VSV). Release of unusual particles with low infectivity. Virology 101:399–407
Maheshwari RK, Banerjee DK, Waechter CJ, Olden K, Friedman RM (1980 a) Interferon treatment inhibits glycosylation of a viral protein. Nature 287:454–456
Maheshwary RK, Demsey AE, Mohanty SB, Friedman RM (1980b) Interferon treated cells release vesicular stomatitis virus particles lacking glycoprotein spikes: Correlation with biochemical data. Proc Natl Acad Sci USA 77:2284–2287
Martin EM, Birsdall NJM, Brown RE, Kerr IM (1979) Enzymic synthesis, characterization and nuclear magnetic resonance spectra of pppA2′p5′A2′p5′A and related oligonucleotides: Comparison with chemical synthesized material. Eur J Biochem 95:295–307
Minks MA, Benvin S, Maroney PA, Baglioni C (1979 a) Synthesis of 2′5′oligo(A) in extracts of interferon-treated HeLa cells. J Biol Chem 254:5058–5064
Minks MA, Benvin S, Maroney PA, Baglioni C (1979 b) Metabolic stability of 2′5′oligo(A) and activity of 2′5′oligo(A)-dependent endonuclease in extracts of control and interferon-treated HeLa cells. Nucleic Acids Res 6:767–780
Minks MA, West DK, Benvin S, Baglioni C (1979 C) 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 254:10180–10183
Minks MA, Benvin S, Baglioni C (1980) Mechanism of pppA(2′p5′A)n2′p5′AOH synthesis in extracts of interferon-treated HeLa cells. J Biol Chem 255:5031–5035
Nilsen TW, Baglioni C (1979) A mechanism for discrimination between viral and host mRNA in interferon-treated cells. Proc Natl Acad Sci USA 76:2600–2604
Nilsen TW, Maroney PA, Baglioni C (1979) 2′5′oligo(A): a mediator of viral RNA cleavage in Interferon-treated cells? In: Koch H, Richter D (eds) Regulation of macromolecular synthesis by low molecular weight mediators. Academic, New York, pp 329–339
Nilsen TW, Weissman SG, Baglioni C (1980) Role of 2′5′-oligo(A) polymerase in the degradation of RNA linked to double-stranded RNA by extracts of interferon-treated cells. Biochemistry 19:5574–5579
Nilsen TW, Maroney PA, Baglioni C (1981 a) Double-stranded RNA causes synthesis of 2′,5′-oligo(A) and degradation of messenger RNA in interferon-treated cells. J Biol Chem 256:7806–7812
Nilsen TW, Wood DL, Baglioni C (1981 b) 2′5′-oligo(A)-activated endoribonuclease. Tissue distribution and characterization with a binding assay. J Biol Chem 256:10751–10754
Nilsen TW, Wood DL, Baglioni C (1981 b) Cross-linking of viral RNA by 4′-aminomethyl-4, 5′,8-trimethylpsoralen in HeLa cells infected with Encephalomyocarditis virus and the tsG114 mutant of vesicular stomatitis virus. Virology 109:82–93
Nilsen TW, Maroney PA, Baglioni C (1982) Synthesis of (2′–5′)oligo(A) and activation of an endoribonuclease in interferon-treated HeLa cells infected with reovirus. J Virol 42:1039–1045
Olden K, Bernard BA, Turner W, White SL (1982) Effect of interferon on protein glycosy-lation and comparison with tunicamycin. Nature 300:290–292
Ratner L, Wiegand RC, Farrell PJ, Sen GC, Cabrer B, Lengyel P (1978) Interferon, double-stranded RNA and RNA degradation, fractionation of the endonuclease system into two macromolecular components; Role of a small molecule in nuclease activation. Biochem Biophys Res Commun 81:947–954
Roberts WK, Hovanessian A, Brown RE, Clemens MJ, Kerr IM (1976) Interferon-mediated protein kinase and low-molecular weight inhibitor of protein synthesis. Nature 264–477–480
Rubin BY, Gupta SL (1980) Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents. Proc Natl Acad Sci USA 77:5928–5932
Samantha H, Dougherty JP, Lengyel P (1980) Synthesis of (2′–5′)An from ATP. J Biol Chem 255:9807–9813
Schmidt A, Zilberstein A, Shulman L, Federman P, Berissi H, Revel M (1978) Interferon action: isolation of nuclease F, a translation inhibitor activated by interferon-induced (2′–5′)oligo-isoadenylate. FEBS Lett 95:257–264
Schmidt A, Chernajovsky Y, Shulman L, Federman P, Berissi H, Revel M (1979) An interferon-induced phosphodiesterase degrading (2′–5′)oligoisoadenylate and the C-C-A terminus of tRNA. Proc Natl Acad Sci USA 76:4788–4792
Sen GC, Lebleu B, Brown GE, Rebello MA, Furuichi H, Morgan M, Shatkin AJ, Lengyel P (1975) Inhibition of reovirus messenger RNA methylation in extracts of interferon-treated Ehrlich ascites tumor cells. Biochem Biophys Res Commun 65–427–434
Sen GC, Lebleu B, Brown GE, Kawakita M, Slattery E, Lengyel P (1976) Interferon, double-stranded RNA and mRNA degradation. Nature 264:370–372
Sen GC, Shaila S, Lebleu B, Brown GE, Desrosierd RC, Lengyel P (1977) Impairment of reovirus mRNA methylation in extracts of interferon-treated Ehrlich ascites tumor cells: further characteristics of the phenomenon. J Virol 21:69–83
Sen GC, Taira H, Lengyel P (1978) Characteristics of a double-stranded RNA-activated protein kinase system partially purified from interferon-treated Ehrlich ascites tumor cells. J Biol Chem 253:5915–5921
Silverman RH, Wreschner DH, Gilbert CS, Kerr IM (1981) Synthesis, characterization and properties of ppp(A2′p)nApCp and related high specificactivity 32P-labelled derivatives of ppp(A2′p)An. Eur J Biochem 115:79–85
Slattery E, Ghosh N, Samantha H, Lengyel P (1979) Interferon, double-stranded RNA, and RNA degradation: Activation of an endonuclease by (2′–5′)An. Proc Natl Acad Sci USA 76:4778–4782
Stark GR, Dower WJ, Schimke RT, Brown RE, Kerr IM (1979) pppA2′p5′A2′p5′A synthetase: Convenient assay, species and tissue distribution and variation upon withdrawal of oestrogen from chick oviducts. Nature 278:471–473
Testa D, Banerjee AK (1977) Two methyltransferase activities in the purified virions of vesicular stomatitis virus. J Virol 24:786–793
West DK, Baglioni C (1979) Induction by interferon of a protein kinase activated by double-stranded RNA in HeLa cells. Eur J Biochem 101:461–468
Williams BRG, Kerr IM, Gilbert CS, White CN, Ball LA (1978) Synthesis and breakdown auf pppA2′p5′A2′p5′A and transient inhibition of protein synthesis in extracts from in-terferon-treated and control cells. Eur J Biochem 92:455–462
Williams BRG, Golgher RR, Brown RE, Gilbert CS, Kerr IM (1979) Natural occurrence of 2–5A in interferon-treated EMC virus-infected L cells. Nature 282:582–586
Wreschner DH, James TC, Silverman RH, Kerr IM (1981) Ribosomal RNA cleavage, nuclease activation and 2–5A (ppp(A2′p)nA in interferon-treated cells. Nucleic Acids Res 9:1571–1581
Zilberstein A, Kimchi A, Schmidt A, Revel M (1978) Isolation of two interferon-induced translational inhibitors: a protein kinase and an oligoisoadenylate synthetase. Proc Natl Acad Sci USA 75:4743–4738
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Baglioni, C. (1984). The Molecular Mediators of Interferon Action. In: Came, P.E., Carter, W.A. (eds) Interferons and Their Applications. Handbook of Experimental Pharmacology, vol 71. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69178-2_8
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DOI: https://doi.org/10.1007/978-3-642-69178-2_8
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