1887

Abstract

The individual and synergistic antiviral effects of cytokines released by infiltrating immune cells or by cells of the nervous system may play an important role in inhibiting virus spread during infections of the central nervous system (CNS). We examined the antiviral activity against the neurotropic pseudorabies virus (PRV) of interferon- (IFN-) and tumour necrosis factor- (TNF-), and combinations of these cytokines, as compared to that of IFN-, in rat nervous tissue cells. PRV replicated efficiently in all neural cell types tested, including neurons, astrocytes and oligodendrocytes. The inhibitory effects were determined by quantifying the inhibition of virus plaque formation, yields of infectious virus at various times after infection and synthesis of viral proteins. At a low m.o.i., IFN- and IFN- inhibited viral plaque formation in all cell types; TNF- was effective only in astrocytes but showed synergy with IFN-. At a higher m.o.i., IFN- inhibited yields of infectious virus more effectively than IFN-, whereas TNF- had no effect on virus yields and was only marginally synergistic with the antiviral activity of IFN-. The yield-reduction assays correlated well with cytokine-induced inhibition of viral protein synthesis. Our results show that both IFN- and IFN- can induce a state of antiviral resistance in neural cells whereas TNF- is effective only in astrocytes at low m.o.i.; they suggest an antiviral role of cytokines in the immune response to virus infections of the CNS.

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1991-04-01
2022-08-11
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References

  1. Aderka D., Novick D., Hahn T., Fisher D. G., Wallach D. 1985; Increase in vulnerability to lymphotoxin in cells infected by vesicular stomatitis virus and its further augmentation by interferon. Cellular Immunology 92:218–225
    [Google Scholar]
  2. Bennink J. R., Yedwell Y. W., Feldman A., Gerhard W., Doherty P. 1985; The role of virus-specific CTL in vivo . In T Cell Clones pp 237–242 Edited by Von Boehmer H., Haas W. Amsterdam: Elsevier;
    [Google Scholar]
  3. Bigami A., Eng L. F., Dahl D., Uyeda C. T. 1972; Localization of the glial fibrillary acidic protein in astrocytes by immunofluorescence. Brain Research 43:429–435
    [Google Scholar]
  4. Bottenstein J. F., Sato G. 1979; Growth of a neuroblastoma cell line in serum-free supplemented medium. Proceedings of the National Academy of Sciences, U.S.A 76:514–517
    [Google Scholar]
  5. Dukema R., Van der Meide P. H., Powells P. H., Caspers M., Dubbeld M., Schellekens H. 1985; Cloning and expression of the chromosomal immune interferon gene of the rat. EMBO Journal 4:761–767
    [Google Scholar]
  6. Epstein L. B., Stevens D. A., Merigan T. C. 1972; Selective increase in lymphocyte interferon response to vaccinia antigen after reactivation. Proceedings of the National Academy of Sciences, U.S.A 69:2632–2636
    [Google Scholar]
  7. Feduchi E., Alonso M. A., Carrasco L. 1989; Human gamma interferon and tumor necrosis factor exert a synergistic blockade on the replication of herpes simplex virus. Journal of Virology 63:1354–1359
    [Google Scholar]
  8. Fierz W., Fontana A. 1986; The role of astrocytes in the interaction between the immune and nervous system. In Cellular Neurobiology: Astrocytes: Cell Biology and Pathology of Astrocytes pp 203–229 Edited by Fedoroff S., Vemadakis A. New York & London: Academic Press;
    [Google Scholar]
  9. Frei K., Bodmer S., Schwerdel C., Fontana A. 1986; Astrocyte-derived interleukin 3 as a growth factor for microglial cells and peritoneal macrophages. Journal of Immunology 137:3521–3527
    [Google Scholar]
  10. Frei K., Leist T. P., Meager A., Gallo P., Leppert D., Zinkernagel R. M., Fontana A. 1988; Production of B cell stimulatory factor 2 and interferon-y in the central nervous system during viral meningitis and encephalitis. Evaluation in a murine model infection and in patients. Journal of Experimental Medicine 168:449–453
    [Google Scholar]
  11. Frei K., Siepl C., Groscurth P., Bodmer S., Schwerdel C., Fontana A. 1987; Antigen presentation and tumour cytotoxicity by interferon-y treated microglial cells. European Journal of Immunology 17:1271–1278
    [Google Scholar]
  12. Frohman E. M., Frohman T. C., Dustin M. L., Vayuvela B., Choi B., Gupta A., Van den Noort S., Gupta S. 1989; The induction of intracellular adhesion molecule 1 (ICAM-1) expression of human fetal astrocytes by interferon-γ, tumor necrosis factor a, lymphotoxin, and interleukin-1: relevance to intracerebral antigen presentation. Journal of Neuroimmunology 23:117–124
    [Google Scholar]
  13. Handa K., Suzuki R., Matsui H., Shimizu Y., Kumagai K. 1983; Natural killer (NK) cells as a responder to interleukin 2 (IL 2). II. IL-2-induced interferon-γ production. Journal of Immunology 130:988–992
    [Google Scholar]
  14. Hofman F. M., Hinton D. R., Johnson K., Merrill J. E. 1989; Tumor necrosis factor identified in multiple sclerosis brain. Journal of Experimental Medicine 170:607–612
    [Google Scholar]
  15. Koper J. W., Hoeben R. C., Hochstenbach F. M. H., Van Golde L. M. G., Lopes Cardozo M. 1986; Effects of triiodothyronine on the synthesis of sulfolipids by oligodendrocyte-enriched glial cell cultures. Biochimica et biophysica acta 887:327–334
    [Google Scholar]
  16. Koper J. W., Lopes Cardozo M., Romijn H. J., Van Golde L. M. G. 1984; Culture of rat cerebral oligodendrocytes in a serum-free chemically defined medium. Journal of Neuroscience Methods 10:157–169
    [Google Scholar]
  17. Lebon P., Boutin B., Dulac O., Ponsot G., Arthuis M. 1989; Interferon-γ in acute and subacute encephalitis. British Medical Journal 296:9–11
    [Google Scholar]
  18. Leist T. P., Eppler M., Zinkernagel R. M. 1989; Enhanced virus replication and inhibition of lymphocytic choriomeningitis virus disease in anti-gamma interferon-treated mice. Journal of Virology 63:2813–2819
    [Google Scholar]
  19. Lewis J. A. 1982; The mechanism of action of interferon. In Horizons in Biochemistry and Biophysics p 357 Edited by Kohn L., Friedman R. New York: John Wiley;
    [Google Scholar]
  20. Lieberman A. P., Pitha P. M., Shin H. S., Shin M. L. 1989; Production of tumour necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus. Proceedings of the National Academy of Sciences, U.S.A 86:6348–6352
    [Google Scholar]
  21. Ljungdahl A., Olsson T., Hojeberg B., Van der Meide P. H., Holmdahl R., Klareskog L. 1989; Interferon-gamma like immunoreactivity in certain neurons of the central and peripheral nervous system. Journal of Neuroscience Research 124:451–456
    [Google Scholar]
  22. Mestan J., Digel W., Mittnacht S., Hillen H., Blohm D., Moller A., Jacobson H., Kirchner H. 1986; Antiviral effects of recombinant tumour necrosis factor in vitro . Nature, London 323:815–819
    [Google Scholar]
  23. Morris A. G., Lin Y. L., Askonas B. A. 1982; Immune interferon release when a cytotoxic T-cell line meets its correct influenza-infected target cells. Nature, London 295:150–152
    [Google Scholar]
  24. Noble M., Murray K. 1984; Purified astrocytes promote the in vitro division of a potential glial progenitor cell. EMBO Journal 3:2243–2247
    [Google Scholar]
  25. Oldstone M. B. A., Blount P., Southern P. J., Lampert P. W. 1986; Cytoimmunotherapy for persistent virus infections reveals a unique clearance pattern from the central nervous system. Nature, London 321:239–242
    [Google Scholar]
  26. O’Malley J. A., Nussbaum-Blumenson A., Sheedy D., Grossmayer B. J., Olzer H. 1982; Identification of the T cell subset that produces human γ interferon. Journal of Immunology 126:2522–2526
    [Google Scholar]
  27. Paya C. V., Kenmotsu N., Schoon R. A., Leibson P. J. 1989; Tumor necrosis factor and lymphotoxin secretion by human natural killer cells leads to antiviral cytotoxicity. Journal of Immunology 141:1989–1995
    [Google Scholar]
  28. Pulliam L., Panitch H. S., Baringer J. R., Dix R. D. 1986; Effect of antiviral agents on replication of herpes simplex virus type 1 in brain cultures. Antimicrobial Agents and Chemotherapy 30:840–846
    [Google Scholar]
  29. Raff H. C., Miller R. H., Noble M. 1983; A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on the culture medium. Nature, London 303:390–396
    [Google Scholar]
  30. Righi M., Mori L., De Libero G., Sironi M., Biondi A., Mantovani A., Denis Donini S., Ricciardi-Castagnoli P. 1989; Monokine production by microglial cell clones. European Journal of Immunology 19:143–148
    [Google Scholar]
  31. Schellekens H., De Wilde G. A., Weimar W. 1980; Production and initial characterization of rat interferon. Journal of General Virology 46:243–247
    [Google Scholar]
  32. Schijns V. E. C., Haagmans B. L., Schellekens H., Horzinek M. C. 1989; Protection of rats against pseudorabies virus infection by γ-interferon. Proceedings of the Society for Experimental Biology and Medicine 192:47–55
    [Google Scholar]
  33. Schijns V., Van Giersbergen P., Schellekens H., Horzinek M. C. 1990; Interferon-gamma applied to the brain ventricular system protects rats against pseudorabies. Journal of Neuroimmunology 28:1–7
    [Google Scholar]
  34. Sethi K. K., Omata Y., Schneweis K. E. 1983; Protection of mice from fatal herpes simplex virus type 1 infection by adoptive transfer of cloned virus-specific and H-2-restricted cytotoxic T lymphocytes. Journal of General Virology 64:443–447
    [Google Scholar]
  35. Starr S. E., Dalton B., Garrabrant T., Paucker K., Plotkin S. A. 1980; Lymphocyte blastogenesis and interferon production in adult human leucocyte cultures stimulated with cytomegalovirus antigens. Infection and Immunity 30:17–22
    [Google Scholar]
  36. Stitz L., Schellekens H. 1980; Influence of input of infection on the antiviral activity of interferon. Journal of General Virology 46:205–210
    [Google Scholar]
  37. Sussman M. A., Shubn R. A., Kyuwa S., Stohlman S. A. 1989; T-cell mediated clearance of mouse hepatitis virus strain JHM from the central nervous system. Journal of Virology 63:3051–3056
    [Google Scholar]
  38. Svennerholm B., Ziegler R., Lycke E. 1989; Herpes simplex virus infection of the rat sensory neuron. Effects of interferon on cultured cells. Archives of Virology 104:153–156
    [Google Scholar]
  39. Tedeschi B., Barrett J. N., Keane R. W. 1986; Astrocytes produce interferon that enhances the expression of H-2 antigens on a subpopulation of brain cells. Journal of Cell Biology 102:2244–2253
    [Google Scholar]
  40. Traugott U., Lebon P. 1988; Multiple sclerosis: involvement of interferons in lesion pathogenesis. Annals of Neurology 24:243–251
    [Google Scholar]
  41. Valle M. J., Bobrove A. M., Strober S., Merigan T. C. 1975; Immune specific production of interferon by human T cells in combined macrophage lymphocyte cultures in response to herpes simplex antigen. Journal of Immunology 144:435–441
    [Google Scholar]
  42. Van der Meide P. H., Dubbeld M., Vijverberg K., Kos T., Schellekens H. 1986; The purification and characterization of rat gamma interferon by use of two monoclonal antibodies. Journal of General Virology 67:1059–1071
    [Google Scholar]
  43. Van der Neut R., Bar P. R., Sodaar P., Gispen W. H. 1988; Trophic influences of alpha-MSH and ACTH4-10 on neuronal outgrowth in vitro . Peptides 9:1015–1020
    [Google Scholar]
  44. Van der Neut R., Oestricher A. B., Gispen W. H., Bar P. R. 1990; The expression of B-50/GAP-43 during development of rat spinal neurons in culture is regulated by intemeuronal contact. Neuroscience Letters 109:36–41
    [Google Scholar]
  45. Wong G. H. W., Goeddel D. V. 1986; Tumour necrosis factor α and β inhibit virus replication and synergize with interferons. Nature, London 323:819–822
    [Google Scholar]
  46. Wong G. H. W., Krowka J. F., Stites D. P., Goeddel D. V. 1988; In vitro anti-human immunodeficiency virus activities of tumor necrosis factor-α and interferon-γ . Journal of Immunology 140:120–124
    [Google Scholar]
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