1887

Abstract

Surmmary

A novel replicating agent (IFDO) was isolated from ileal fluid. Growth occurred under aerobic and anaerobic conditions, and was faster at 37°C than at room temperature. The doubling time was 15.8 min. Colonies were dark brown in colour and occurred beneath the surface of agar after conventional surface inoculation. Provisional data indicate that the agent may be a normal intestinal commensal. The agent was remarkably resistant to inactivation by steam at 134°C, formaldehyde and glutaraldehyde; it was relatively resistant to ionising radiation, and it was filterable through membranes with a nominal pore diameter of 10 nm. Such properties, with the exception of growth in cell-free medium, are shared by “unconventional agents” such as those of Creutzfeldt-Jakob disease and scrapie. Further comparison of the properties of the intestinal agent and of slow viruses revealed additional shared characteristics, including resistance to proteinase K and trypsin, and inactivation by guanidine thiocyanate, diethyl pyrocarbonate, phenol and sodium hydroxide. The agent differs from that of scrapie in being inactivated by ethidium bromide, zinc nitrate, EDTA, hydroxylamine in the presence Sarkosyl, and, under certain circumstances, by ribonuclease. Broth cultures of the agent contained particles possessing considerable size heterogeneity. The smaller filterable particles were generally more susceptible to inactivation, did not survive autoclaving, and were inactivated by papaya protease and lipase. It is possible that the replicating agent may be formed by crystallisation from constituents of the medium, and not by a biological process. This does not exclude the postulated relationship to slow viruses.

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1989-06-01
2022-10-03
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References

  1. Alper T., Haig D. A., Clarke M. C. 1966; The exceptionally small size of the scrapie agent. Biochemical and Biophysical Research Communications 22:278–284
    [Google Scholar]
  2. Alper T., Cramp W. A., Haig D. A., Clarke M. C. 1967; Does the agent of scrapie replicate without nucleic acid?. Nature 214:764–766
    [Google Scholar]
  3. Alper T., Haig D. A., Clarke M. C. 1978; The scrapie agent:evidence against its dependence for replication on intrinsic nucleic acid. Journal of General Virology 41:503–516
    [Google Scholar]
  4. Bignami A., Parry H. B. 1971; Aggregation of 35-nanometer particles associated with neuronal cytopathic changes in natural scrapie. Science 171:389–390
    [Google Scholar]
  5. Bockman J. M., Kingsbury D. T., McKinley M. P., Brendheim P. E., Prusiner S. B. 1985; Creutzfeldt-Jakob disease prion proteins in human brains. New England Journal of Medicine 312:73–78
    [Google Scholar]
  6. Brown P. 1982a; Chemical disinfection of Creutzfeldt-Jakob disease virus. New England Journal of Medicine 306:1279–1282
    [Google Scholar]
  7. Brown P., Rohwer R. G., Green E. M., Gajdusek D. C. 1982b; Effect of chemicals, heat, and histopathologic processing on high-infectivity hamster-adapted scrapie virus. Journal of Infectious Diseases 145:683–687
    [Google Scholar]
  8. Brown P., Rohwer R. G., Gajdusek D. C. 1986; Newer data on the inactivation of Scrapie virus or Creutzfeldt-Jakob disease virus in brain tissue. Journal of Infectious Diseases 153:1145–1148
    [Google Scholar]
  9. Butzow J. J., Eichhom G. L. 1975; Different susceptibility of DNA and RNA to cleavage by metal ions. Nature 254:358–359
    [Google Scholar]
  10. Connors L. H., Shirahama T., Skinner M., Fenves A., Cohen A. S. 1985; In vitro formation of amyloid fibrils from intact ß 2-microglobulin. Biochemical and Biophysical Research Communications 131:1063–1068
    [Google Scholar]
  11. Gajdusek D. C. 1977; Unconventional viruses and the origin and disappearance of kuru. Science 197:943–960
    [Google Scholar]
  12. Gajdusek D. C. 1977; Precaution in medical care of, and in handling materials from, patients with transmissible virus dementia (Creutzfeldt-Jakob disease). New England Journal of Medicine 297:1253–1258
    [Google Scholar]
  13. Gibbs C. T., Gajdusek D. C., Latarjet R. 1978; Unusual resistance to ionizing radiation of the viruses of kuru, Creutzfeldt-Jakob disease, and scrapie. Proceedings of the National Academy of Science of the USA 75:6268–6270
    [Google Scholar]
  14. Glenner G. G., Ein D., Eanes E. D., Bladen H. A., Terry W., Page D. L. 1971; Creation of “amyloid” fibrils from Bence Jones Protein in vitro. Science 174:712–714
    [Google Scholar]
  15. Kimberlin R. H. 1982; Scrapie agent:prions or virinos?. Nature 297:107–108
    [Google Scholar]
  16. Kochetkov N. K., Budowsky E. I. 1969; The chemical modification of nucleic acids. Progress in Nucleic Acid Research and Molecular Biology 9:403–438
    [Google Scholar]
  17. Marsh R. F., Malone T. G., Semancik J. S., Lancaster W. D., Hanson R. P. 1978; Evidence for an essential DNA component in the scrapie agent. Nature 275:146–147
    [Google Scholar]
  18. McKinley M. P., Masiarz F. R., Prusiner S. B. 1981; Reversible chemical modification of the scrapie agent. Science 214:1259–1261
    [Google Scholar]
  19. McKinley M. P., Braunfeld M. B., Bellinger C. G., Prusiner S. B. 1986; Molecular characteristics of prion rods purified from scrapie-infected hamster brains. Journal of Infectious Diseases 154:110–120
    [Google Scholar]
  20. Oesch B. 1985; A cellular gene encodes scrapie PrP 27–30 protein. Cell 40:735–746
    [Google Scholar]
  21. Pattison I. H. 1965; Resistance of the scrapie agent to formalin. Journal of Comparative Pathology 75:159–164
    [Google Scholar]
  22. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
    [Google Scholar]
  23. Prusiner S. B. 1984; Some speculation about prions, amyloid and Alzheimer’s disease. New England Journal of Medicine 310:661–663
    [Google Scholar]
  24. Prusiner S. B. 1987; Prions and neurodegenerative diseases. New England Journal of Medicine 317:1571–1581
    [Google Scholar]
  25. Prusiner S. B., Hadlow W. J., Eklund C. M., Race R. E., Cochran S. P. 1978a; Sedimentation characteristics of the scrapie agent from murine spleen and brain. Biochemistry 17:4987–4992
    [Google Scholar]
  26. Prusiner S. B. 1978b; Partial purification and evidence for multiple molecular forms of the scrapie agent. Biochemistry 17:4993–4999
    [Google Scholar]
  27. Prusiner S. B. 1980a; Experimental scrapie in the mouse:electrophoretic and sedimentation properties of the partially purified agent. Journal of Neurochemistry 35:574–582
    [Google Scholar]
  28. Prusiner S. B., Groth D. F., Cochran S. P., Masiarz F. R., McKinley M. P., Martinez H. M. 1980b; Molecular properties, partial purification and assay by incubation period measurements of the hamster scrapie agent. Biochemistry 19:4883–4891
    [Google Scholar]
  29. Prusiner S. B., Groth D. F., McKinley M. P., Cochran S. P., Bowman K. A., Kasper K. C. 1981; Thiocyanate and hydroxyl ions inactivate the scrapie agent. Proceedings of the National Academy of Science of the USA 78:4606–4610
    [Google Scholar]
  30. Prusiner S. B., Bolton D. C., Groth D. F., Bowman K. A., Cochran S. P., McKinley M. P. 1982; Further purification and characterization of scrapie prions. Biochemistry 21:6942–6950
    [Google Scholar]
  31. Prusiner S. B. 1983; Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 35:349–358
    [Google Scholar]
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