1887

Abstract

The protease-resistant isoform of prion protein (PrP) has been implicated in the pathogenesis and transmission of Creutzfeldt-Jakob disease (CJD), scrapie and other related diseases, but the relationship between the infectious agent and PrP awaits elucidation. In the present study, we have examined levels of infectivity together with accumulation of the protease-resistant form of PrP (PrP) in various tissues of CJD agent-inoculated mice. Accumulation of PrP occurred only in tissues, including brain, salivary gland and spleen, in which infectivity was readily detectable throughout the course of the experiment. The brain showed the highest levels of both infectivity and PrP accumulation, with well correlated kinetics. On the other hand, the high titres of infectivity detected in salivary gland and spleen early after inoculation of the agent were obviously distinguishable from PrP. Furthermore, in the salivary gland, the kinetics of infectivity and the accumulation of PrP reversed; infectivity declined as PrP accumulated in the tissue. Our findings indicate that PrP accumulation is associated with replication of the agent; however, PrP is unlikely to be the agent itself.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-74-10-2117
1993-10-01
2022-08-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/74/10/JV0740102117.html?itemId=/content/journal/jgv/10.1099/0022-1317-74-10-2117&mimeType=html&fmt=ahah

References

  1. Bendheim P. E., Barry R., DeArmond S. J., Stites D. P., Prusiner S. B. 1984; Antibodies to a scrapie prion protein. Nature, London 310:418–421
    [Google Scholar]
  2. Bessen R. A., Marsh R. F. 1992; Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. Journal of Virology 66:2096–2101
    [Google Scholar]
  3. Büeler H., Fischer M., Lang Y., Bluethmann H., Lipp H. -P., DeArmond S. J., Prusiner S. B., Aguet M., Weissmann C. 1992; Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein. Nature, London 356:577–582
    [Google Scholar]
  4. Chandler R. L. 1961; Encephalopathy in mice produced by inoculation with scrapie brain material. Lancet i:1378–1379
    [Google Scholar]
  5. Chesebro B., Race R., Wehrly K., Nishio J., Bloom M., Lechner D., Bergstrom S., Robbins K., Mayer L., Keith J. M., Garon C., Haase A. 1985; Identification of scrapie prion protein-specific mRNA in scrapie-infected and uninfected brain. Nature, London 315:331–333
    [Google Scholar]
  6. Czub M., Braig H. R., Diringer H. 1986; Pathogenesis of scrapie: study of the temporal development of clinical symptoms, of infectivity titres and scrapie-associated fibrils in brains of hamsters infected intraperitoneally. Journal of General Virology 61:2005–2009
    [Google Scholar]
  7. Czub M., Braig H. R., Diringer H. 1988; Replication of the scrapie agent in hamsters infected intracerebrally confirms the pathogenesis of an amyloid-inducing virosis. Journal of General Virology 69:1753–1756
    [Google Scholar]
  8. Dickinson A. G., Outram G. W. 1988; Genetic aspects of unconventional virus infection: the basis of the virino hypothesis. Ciba Foundation Symposium 135:63–83
    [Google Scholar]
  9. Eklund C. M., Kennedy R. C., Hadlow W. J. 1967; Pathogenesis of scrapie virus infection in the mouse. Journal of Infectious Diseases 117:15–22
    [Google Scholar]
  10. Gajdusek D. C., Gibbs C. J., Alpers M. 1966; Experimental transmission of a kuru-like syndrome to chimpanzees. Nature, London 209:794–796
    [Google Scholar]
  11. Gibbs C. J. Jr, Gajdusek D. C., Asher D. M., Alpers M. P., Beck D., Daniel P. M., Matthews W. B. 1968; Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science 161:388–389
    [Google Scholar]
  12. Hsiao K. K., Scott M., Foster D., Groth D. F., DeArmond S. J., Prusiner S. B. 1990; Spontaneous neurodegeneration in transgenic mice with mutant prion protein. Science 250:1587–1590
    [Google Scholar]
  13. Kärber V. G. 1931; Beitrag zur kollektiven Behandlung pharma-kologischer Reihenversuche. Archiv für experimentelle Pathologie und Pharmakologie 162:480–483
    [Google Scholar]
  14. Kimberlin R. H., Walker C. A. 1989; The role of the spleen in the neuroinvasion of scrapie in mice. Virus Research 12:201–212
    [Google Scholar]
  15. Kitamoto T., Mohri S., Tateishi J. 1989; Organ distribution of proteinase-resistant prion protein in humans and mice with Creutzfeldt-Jakob disease. Journal of General Virology 70:3371–3379
    [Google Scholar]
  16. Kuroda T., Gibbs C. J. Jr, Amyx H. L., Gajdusek D. C. 1983; Creutzfeldt-Jakob disease in mice: persistent viremia and preferential replication of virus in low-density lymphocytes. Infection and Immunity 41:154–161
    [Google Scholar]
  17. Laemmli U. K. 1970; Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, London 227:680–685
    [Google Scholar]
  18. Manuelidis L., Sklaviadis T., Manuelidis E. E. 1987; Evidence suggesting that PrP is not the infectious agent in Creutzfeldt-Jakob disease. EMBO Journal 6:341–347
    [Google Scholar]
  19. Marsh R. F., Kimberlin R. H. 1975; Comparison of scrapie and transmissible mink encephalopathy in hamsters; clinical signs, pathology, and pathogenesis. Journal of Infectious Diseases 131:104–110
    [Google Scholar]
  20. Oesch B., Westaway D., Wälchli M., McKinley M. P., Kent S. B. H., Aebersold R., Barry R. A., Tempst P., Teplow D. B., Hood L. E., Prusiner S. B., Weissman C. 1985; A cellular gene encodes scrapie PrP 27-30 protein. Cell 40:735–746
    [Google Scholar]
  21. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
    [Google Scholar]
  22. Prusiner S. B. 1991; Molecular biology of prion diseases. Science 252:1515–1522
    [Google Scholar]
  23. Prusiner S. B., DeArmond S. J. 1990; Prion diseases of the central nervous system. Monographs in Pathology/International Academy of Pathology Monograph 32:86–122
    [Google Scholar]
  24. Prusiner S. B., Groth D. F., Cochran S. P., Masiartz F. R., McKinley M. P., Martinez H. M. 1980; Molecular properties, partial purification, and assay by inoculation period measurements of the hamster scrapie agent. Biochemistry 19:4883–4891
    [Google Scholar]
  25. Prusiner S. B., McKinley M. P., Bowman K. A., Bolton D. C., Bendheim P. E., Groth D. F., Glenner G. G. 1983; Scrapie prions aggregate to form amyloid-like birefringent rods. Cell 35:349–358
    [Google Scholar]
  26. Prusiner S. B., Scott M., Foster D., Pan K.-M., Groth D., Mirenda C., Torchia M., Yang S.-L., Serban D., Carlson G. A., Hoppe P. C., Westaway D., DeArmond S. J. 1990; Transgenic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63:673–686
    [Google Scholar]
  27. Race R. E., Ernst D. 1992; Detection of proteinase K-resistant prion protein and infectivity in mouse spleen by 2 weeks after scrapie agent inoculation. Journal of General Virology 73:3319–3323
    [Google Scholar]
  28. Rubenstein R., Merz P. A., Kascsak R. J., Scalici C. L., Papini M. C., Carp R. I., Kimberlin H. 1991; Scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and protease-resistant proteins. Journal of Infectious Diseases 164:29–35
    [Google Scholar]
  29. Shinagawa M., Munekata E., Doi S., Takahashi K., Goto H., Sato G. 1986; Immunoreactivity of synthetic pentadecapeptide corresponding to the N-terminal region of the scrapie prion protein. Journal of General Virology 67:1745–1750
    [Google Scholar]
  30. Takahashi K., Shinagawa M., Doi S., Sasaki S., Goto H., Sato G. 1986; Purification of scrapie agent from infected animal brains and raising of antibodies to the purified fraction. Microbiology and Immunology 30:123–131
    [Google Scholar]
  31. Tateishi J., Ohta M., Koga M., Sato Y., Kuroiwa Y. 1979; Transmission of chronic spongiform encephalopathy with kuru plaques from humans to small rodents. Annals of Neurology 5:581–584
    [Google Scholar]
  32. Towbin H., Staehelin T., Gordon J. 1979; Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proceedings of the National Academy of Sciences, U. S. A 76:4350–4354
    [Google Scholar]
  33. Weissmann C. 1991a; The prion’s progress. Nature, London 349:569–571
    [Google Scholar]
  34. Weissmann C. 1991b; A ‘unified theory’ of prion propagation. Nature, London 352:679–683
    [Google Scholar]
  35. Xi Y. G., Ingrosso L., Ladogana A., Masullo C., Pocchiari M. 1992; Amphotericin B treatment dissociates in vivo replication of the scrapie agent from PrP accumulation. Nature, London 356:598–601
    [Google Scholar]
  36. Zlotnik I., Rennie J. G. 1965; Experimental transmission of mouse passaged scrapie to goats, sheep, rats and hamsters. Journal of Comparative Pathology 75:147–157
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-74-10-2117
Loading
/content/journal/jgv/10.1099/0022-1317-74-10-2117
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error