1887

Abstract

SUMMARY

Although poly(I) is generally considered to be inactive as an interferon inducer, we have found several authentic poly(I) preparations to be effective inducers. Their interferon inducing ability varied considerably from one cell system to another. In human diploid fibroblasts, primed with interferon and superinduced by cycloheximide and actinomycin D, all active poly(I) samples proved nearly as effective in inducing interferon as poly(I).poly(C). In primary rabbit kidney cell cultures, the active poly(I) samples were either as active, or 3 to 30 times less active than poly(I).poly(C). In intact rabbits they were 100 times less active than poly(I).poly(C). Except for one particular sample, all active poly(I) preparations were inferior to poly(I).poly(C) when assayed for interferon induction in interferon-treated mouse L cells; in DEAE-dextran-treated L cells, they induced little, if any, interferon. The poly(I) inducers of interferon were considerably more susceptible to degradation by T1 ribonuclease, pancreatic ribonuclease and human serum nuclease(s) than was poly(I).poly(C) when assayed under the same conditions. Due to their limited half-life time in biological fluids, poly(I) analogues such as those described here may offer a greater safety margin in clinical use than poly(I).poly(C).

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1978-07-01
2021-10-17
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References

  1. Baron S., Bogomolova N. N., Billiau A., Levy H. B., Buckler C. E., Stern R., Naylor R. 1969; Induction of interferon by preparations of synthetic single-stranded RNA. Proceedings of the National Academy of Sciences of the United States of America 64:67–74
    [Google Scholar]
  2. Beers R. F. Jun 1960; Hydrolysis of polyadenylic acid by pancreatic ribonuclease. Journal of Biological Chemistry 235:2393–2398
    [Google Scholar]
  3. Billiau A., Buckler C. E., Oianzani F., Uhlendorf C., Baron S. 1969; Induction of the interferon mechanism by single-stranded RNA: potentiation by polybasic substances. Proceedings of the Society for Experimental Biology and Medicine 132:790–796
    [Google Scholar]
  4. Carter W. A., O’Malley J., Beeson M., Cunnington P., Kelvin A., Vere-Hodge A., Alderfer J. L., Ts’O P. O. P. 1976; An integrated and comparative study of the antiviral effects and other biological properties of the polyinosinic. polycytidylic acid duplex and its mismatched analogues. III. Chronic effects and immunological features. Molecular Pharmacology 12:440–453
    [Google Scholar]
  5. Carter W. A., Pitha P. M., Marshall L. W., Tazawa I., Tazawa S., Ts’ P. O. P. 1972; Structural requirements of the rIn. rCn., complex for induction of human interferon. Journal of Molecular Biology 70:567–587
    [Google Scholar]
  6. De Clercq E. 1974; Synthetic interferon inducers. Topics in Current Chemistry 52:173–208
    [Google Scholar]
  7. De Clercq E., De Somer P. 1972; Mechanism of the antiviral activity resulting from sequential administration of complementary homopolyribonucleotides to cell cultures. Journal of Virology 9:721–731
    [Google Scholar]
  8. De Clercq E., De Somer P. 1975; Are cytotoxicity and interferon inducing activity of poly (I). poly(C) invariably linked in interferon-treated L cells?. Journal of General Virology 27:35–44
    [Google Scholar]
  9. De Clercq E., Edy V. G., Torrence P. F., Waters J. A., Witkop B. 1976; Antiviral activity of poly (7-deazainosinic acid)-derived complexes in vitro and in vivo. Molecular Pharmacology 12:1045–1051
    [Google Scholar]
  10. De Clercq E., Stewart W. E. II, De Somer P. 1975; In vitro assay for determination of toxicity to antiviral activity ratios of double stranded RNAs. Proceedings of the First Inter sectional Congress of the International Association of Microbiological Societies Science Council of Japan, vol 4: pp 57–61 Edited by Hasegawa T.
    [Google Scholar]
  11. De Clercq E., Torrence P. F. 1977; Comparative study of various double-stranded RNAs as inducers of human interferon. Journal of General Virology 37:619–623
    [Google Scholar]
  12. De Clercq E., Torrence P. F., Witkop B. 1974; Interferon induction by synthetic polynucleotides: importance of purine N-7 and strandwise rearrangement. Proceedings of the National Academy of Sciences of the United States of America 71:182–186
    [Google Scholar]
  13. Dianzani F., Baron S., Buckler C. E., Levy H. B. 1971; Mechanism of DEAE-dextran enhancement of polynucleotide induction of interferon. Proceedings of the Society for Experimental Biology and Medicine 136:1111–1114
    [Google Scholar]
  14. Dianzani F., Cantagalli P., Gagnoni S., Rita G. 1968; Effect of DEAE-dextran on production of interferon induced by synthetic double-stranded RNA in L cell cultures. Proceedings of the Society for Experimental Biology and Medicine 128:708–710
    [Google Scholar]
  15. Field A. K., Tytell A. A., Lampson G. P., Hilleman M. R. 1968; Inducers of interferon and host resistance. V. In vitro studies. Proceedings of the National Academy of Sciences of the United States of America 61:340–346
    [Google Scholar]
  16. Nordlund J. J., Wolff S. M., Levy H. B. 1970; Inhibitors of biologic activity of polyI: polyC by human plasma. Proceedings of the Society for Experimental Biology and Medicine 133:439–444
    [Google Scholar]
  17. Pitha P. M., Pitha J. 1974; Interferon induction by single-stranded polynucleotides modified with poly-bases. Journal of General Virology 24:385–390
    [Google Scholar]
  18. Reuss K., Scheit K.-H., Saiko O. 1976; Induction of interferon by polyribonucleotides containing thiopyrimidines. Nucleic Acids Research 3:2861–2875
    [Google Scholar]
  19. Stern R. 1970; A nuclease from animal serum which hydrolyzes double-stranded RNA. Biochemical and Biophysical Research Communications 41:608–614
    [Google Scholar]
  20. Stewart II W. E., De Clercq E. 1974; Relationship of cytotoxicity and interferon-inducing activity of polyriboinosinic acid.polyribocytidylic acid to the molecular weights of the homopolymers. Journal of General Virology 23:83–89
    [Google Scholar]
  21. Stollar B. D., De Clercq E., Drocourt J.-L., Thang M. N. 1978; Immunochemical measurement of conformational heterogeneity of poly(inosinic) acid. European Journal of Biochemistry 82:339–346
    [Google Scholar]
  22. Thang M. N., Bachner L., De Clercq E., Stollar B. D. 1977; A continuous high molecular weight base-paired structure is not an absolute requirement for a potential polynucleotide inducer of interferon. FEBS Letters 76:159–165
    [Google Scholar]
  23. Ts’O P. O. P., Alderfer J. L., Levy J., Marshall L. W., O’Malley J., Horoszewicz J. S., Carter W. A. 1976; An integrated and comparative study of the antiviral effects and other biological properties of the polyinosinic acid-polycytidylic acid and its mismatched analogues. Molecular Pharmacology 12:299–312
    [Google Scholar]
  24. Tytell A. A., Lampson G. P., Field A. K., Nemes M. M., Hilleman M. R. 1970; Influence of size of individual homopolynucleotides on the physical and biological properties of complexed rIn.rCn (poly I: C). Proceedings of the Society for Experimental Biology and Medicine 135:917–921
    [Google Scholar]
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