1887

Abstract

SUMMARY

Protection of mice against EMC virus infection by poly C and poly I has already been distinguished from interferon mediated protection in several ways. Transfer of serum from EMC virus infected and poly C or poly I treated mice to donor mice that were then infected shows that the anti-viral effect of the single-stranded poly-nucleotides is not due to boosting interferon produced by infection itself in the way that interferon can be ‘primed’ . Mice surviving infections of more than 1 × LD as a result of poly C or poly I treatment show no protection against re-infection 15 days after the first infection, indicating no long-term stimulation of immune responses to the virus. Mice treated with an immunosuppressive regime of cytosine arabinoside can be protected against EMC virus infection with poly C and poly I treatment and athymic ‘nude’ mice can also be protected. The possibility of IgM stimulation by poly C and poly I seems unlikely from experiments in which serum was transferred from mice treated with the polynucleotides and an inactivated EMC ‘vaccine’ to recipient mice which were then challenged with infectious virus.

Protection of mice against EMC virus by the single-stranded polynucleotides is abolished by administration of silica to the mice, implying an involvement of macrophages in the protective effects of poly C and poly I. The possibility that the polynucleotides stimulate clearance of virus particles, at least from immunologically responsive regions of the mouse, has been discounted by the inability of polynucleotide treatment to suppress ‘vaccine’ mediated protection of mice. These results indicate that macrophages are involved in the anti-viral effects of poly C and poly I either because they inhibit replication of the virus in macrophages or because direct anti-viral properties of macrophages are activated by the polynucleotides.

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1976-07-01
2024-12-10
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References

  1. ALEXANDER P., EVANS R. 1971; Endotoxin and double-stranded RNA renders macrophages cytotoxic. Nature New Biology 232:76–78
    [Google Scholar]
  2. ALLISON A. C. 1974; On the role of mononuclear phagocytes in immunity against viruses. Progress in Medical Virology 18:15–31
    [Google Scholar]
  3. ALLISON A. C, HARINGTON J. S., BIRBECK M. 1966; An examination of the cytotoxic effects of silica on macrophages. Journal of Experimental Medicine 124:141–154
    [Google Scholar]
  4. ASKONAS B. A., RHODES J. M. 1965; Immunogenicity of antigen-containing ribonucleic acid preparations from macrophages. Nature, London 250:470–474
    [Google Scholar]
  5. BEYER M. M., FRIEDMAN E. A. 1975; Prolonged survival of rabbit skin and kidney allografts following donor treatment with cytosine arabinoside. Transplantation 19:60–63
    [Google Scholar]
  6. BRADISH C. J., ALLNER K., FITZGEORGE R. 1975; Immunomodification and expression of virulence in mice by defined strains of Semliki Forest virus: the effects of Myocrisin and 1-asparaginase. Journal of General Virology 28:239–250
    [Google Scholar]
  7. CONNORS T. A. 1973; Cytotoxic agents with immunosuppressive activity. Biochemical Society Transactions 1:1049–1054
    [Google Scholar]
  8. DANIELS C. A., BORSOS T., RAPP H. J., SNYDERMAN R., NOTKINS A. L. 1970; Neutralization of sensitized virus by purified components of complement. Proceedings of the National Academy of Sciences, United States of America 65:528–535
    [Google Scholar]
  9. DU BUY H. 1975; Effect of silica on virus infections in mice and mouse tissue culture. Infection and Immunity 11:996–1002
    [Google Scholar]
  10. EUSTATIA J. M., MAASE E., VAN HELDEN P., VAN DER VEEN J. 1972; Viral replication in mouse macrophages. Archiv für die gesamte Virusforschung 39:376–380
    [Google Scholar]
  11. JULLIEN P., DE MAEYER-GUIGNARD J., DE MAEYER E. 1974; Interferon synthesis in X-irradiated animals. V. Origin of mouse serum interferon induced by polyinosinic-polycytidilic acid and encephalomyo-carditis virus. Infection and Immunity 10:1023–1028
    [Google Scholar]
  12. MARGOLIS S. A., OIE H., LEVY H. B. 1972; The effect of interferon, interferon inducers or interferon induced virus resistance on subsequent interferon production. Journal of General Virology 15:119–128
    [Google Scholar]
  13. MIMS C. A. 1964; Aspects of the pathogenesis of viral diseases. Bacteriological Reviews 28:30–71
    [Google Scholar]
  14. PETO R., PIKE M. C. 1973; Conservation of the approximation [i]Σ(0 − E)[sup]2[/sup]/E[/i] in the logrank test for survival data or tumour incidence data. Biometrics 29:579–584
    [Google Scholar]
  15. PORTER A., CAREY V., FELLNER P. 1974; Presence of a large poly(rC) tract within the RNA of encephalo-myocarditis virus. Nature, London 248:675–678
    [Google Scholar]
  16. RAGER-ZISMAN B., ALLISON A. C. 1973; The role of antibody and host cells in the resistance of mice against infection by Coxsackie B-3 virus. Journal of General Virology 19:329–338
    [Google Scholar]
  17. SCHMIDTKE J. R., JOHNSON A. G. 1971; Regulation of the immune system by synthetic polynucleotides. I. Characteristics of adjuvant action on antibody synthesis. Journal of Immunology 106:1191–1200
    [Google Scholar]
  18. STEBBING N., GRANTHAM C. A. 1976; Anti-viral activity against encephalomyocarditis virus and Semliki Forest virus and acute toxicity of poly I and poly C administered sequentially in mice. Archives of Virology in the press
    [Google Scholar]
  19. STEBBING N., GRANTHAM C. A., CAREY V. H. 1976; Anti-viral activity of single-stranded homopolynucleotides against encephalomyocarditis virus and Semliki Forest virus in adult mice without interferon induction. Journal of General Virology 30:21–39
    [Google Scholar]
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