1887

Abstract

Different strains of transmissible spongiform encephalopathies in humans and rodent models are associated with the accumulation of PrP of distinct molecular characteristics. These characteristics include glycosylation profiles, fragment sizes and long-term resistance of PrP to proteinase K. The first objective of this study was to determine the applicability of these criteria to characterize and differentiate sheep scrapie PrP and bovine spongiform encephalopathy (BSE) PrP. PrP in sheep scrapie samples from Ireland had clearly distinct molecular characteristics to PrP in cattle BSE samples using a monoclonal antibody (MAb P4) directed to position 89–104 of ovine PrP using either brain homogenates or semi-purified scrapie-associated fibrils. Similar glycoprofiles were found when analysing scrapie PrP in six different CNS regions (thoracic spinal cord, thalamus, basal ganglia, mediobasal hypothalamus, medulla oblongata and cortex). While the long-term resistance results using a different monoclonal antibody (raised to ruminant PrP positions 145–163; MAb L42) were similar to the results obtained with MAb P4, different glycotyping results were obtained. Given the variation in glycosylation patterns using different antibodies, we conclude that standardization of methodology and antibodies is crucial to the applicability of molecular analysis of ruminant BSE and scrapie samples.

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2000-06-01
2019-10-21
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References

  1. Baron, T. G., Madec, J. Y. & Calavas, D. ( 1999; ). Similar signature of the prion protein in natural sheep scrapie and bovine spongiform encephalopathy-linked diseases. Journal of Clinical Microbiology 37, 3701-3704.
    [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. Bessen, R. A. & Marsh, R. F. ( 1994; ). Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. Journal of Virology 68, 7859-7868.
    [Google Scholar]
  4. Bruce, M. E. & Dickinson, A. G. ( 1987; ). Biological evidence that scrapie agent has an independent genome. Journal of General Virology 68, 79-89.[CrossRef]
    [Google Scholar]
  5. Bruce, M. E., McConnell, I., Fraser, H. & Dickinson, A. G. ( 1991; ). The disease characteristics of different strains of scrapie in Sinc congenic mouse lines: implications for the nature of the agent and host control of pathogenesis. Journal of General Virology 72, 595-603.[CrossRef]
    [Google Scholar]
  6. Bruce, M. E., Will, R. G., Ironside, J. W., McConnell, I., Drummond, D., Suttie, A., McCardle, L., Chree, A., Hope, J., Birkett, C., Cousens, S., Fraser, H. & Bostock, C. J. ( 1997; ). Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389, 498-501.[CrossRef]
    [Google Scholar]
  7. Collinge, J., Sidle, K. C., Meads, J., Ironside, J. & Hill, A. F. ( 1996; ). Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature 383, 685-690.[CrossRef]
    [Google Scholar]
  8. Dickinson, A. G. & Meikle, V. M. H. ( 1971; ). Host-genotype and agent effects in scrapie incubation: change in allelic interaction with different strains of agent. Molecular and General Genetics 112, 73-79.[CrossRef]
    [Google Scholar]
  9. Diringer, H., Hilmert, H., Simon, D., Werner, E. & Ehlers, B. ( 1983; ). Towards purification of the scrapie agent. European Journal of Biochemistry 134, 555-560.[CrossRef]
    [Google Scholar]
  10. Foster, J. D., Hope, J. & Fraser, H. ( 1993; ). Transmission of bovine spongiform encephalopathy to sheep and goats. Veterinary Record 133, 339-341.[CrossRef]
    [Google Scholar]
  11. Fraser, H. & Dickinson, A. G. ( 1973; ). Scrapie in mice. Agent-strain differences in the distribution and intensity of grey matter vacuolation. Journal of Comparative Pathology 83, 29-40.[CrossRef]
    [Google Scholar]
  12. Groschup, M. H. & Pfaff, E. ( 1993; ). Studies on a species-specific epitope in murine, ovine and bovine prion protein. Journal of General Virology 74, 1451-1456.[CrossRef]
    [Google Scholar]
  13. Harmeyer, S., Pfaff, E. & Groschup, M. H. ( 1998; ). Synthetic peptide vaccines yield monoclonal antibodies to cellular and pathological prion proteins of ruminants. Journal of General Virology 79, 937-945.
    [Google Scholar]
  14. Hill, A. F., Desbruslais, M., Joiner, S., Sidle, K. C., Gowland, I., Collinge, J., Doey, L. J. & Lantos, P. ( 1997; ). The same prion strain causes vCJD and BSE. Nature 389, 448-450.[CrossRef]
    [Google Scholar]
  15. Hill, A. F., Sidle, K. C. L., Joiner, S., Keyes, P., Martin, T. C., Dawson, M. & Collinge, J. ( 1998; ). Molecular screening of sheep for bovine spongiform encephalopathy. Neuroscience Letters 255, 159-162.[CrossRef]
    [Google Scholar]
  16. Hope, J., Wood, S. C. E. R., Birkett, C. R., Chong, A., Bruce, M. E., Cairns, D., Goldmann, W., Hunter, N. & Bostock, C. J. ( 1999; ). Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641. Journal of General Virology 80, 1-4.
    [Google Scholar]
  17. Kascsak, R. J., Rubenstein, R., Merz, P. A., Carp, R. I., Wisniewski, H. M. & Diringer, H. ( 1985; ). Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents. Journal of General Virology 66, 1715-1722.[CrossRef]
    [Google Scholar]
  18. Kimberlin, R. H. & Walker, C. A. ( 1978; ). Evidence that the transmission of one source of scrapie agent to hamsters involves separation of agent strains from a mixture. Journal of General Virology 39, 487-496.[CrossRef]
    [Google Scholar]
  19. Kimberlin, R. H., Walker, C. A. & Fraser, H. ( 1989; ). The genomic identity of different strains of mouse scrapie is expressed in hamsters and preserved on reisolation in mice. Journal of General Virology 70, 2017-2025.[CrossRef]
    [Google Scholar]
  20. Kuczius, T. & Groschup, M. H. ( 1999; ). Differences in proteinase K resistance and neuronal deposition of abnormal prion proteins characterize bovine spongiform encephalopathy (BSE) and scrapie strains. Molecular Medicine 5, 406-418.
    [Google Scholar]
  21. Kuczius, T., Haist, I. & Groschup, M. H. ( 1998; ). Molecular analysis of bovine spongiform encephalopathy and scrapie strain variation. Journal of Infectious Diseases 178, 693-699.[CrossRef]
    [Google Scholar]
  22. McElroy, M., Weavers, E., Gomerez Parada, M., Healy, A., Doherty, M., Sweeney, T., O’Doherty, E., Aherne, M., Church, A., Monks, E., Roche, J. F. & Collins, D. J. (2000). Establishment of a tissue bank and database of naturally occurring scrapie in sheep in Ireland. Irish Veterinary Journal (in press).
  23. Oesch, B., Westaway, D., Walchli, M., McKinley, M. P., Kent, S. B., Aebersold, R., Barry, R. A., Tempst, P., Teplow, D. B., Hood, L. E. and others ( 1985; ). A cellular gene encodes scrapie PrP 27–30 protein. Cell 40, 735–746.[CrossRef]
    [Google Scholar]
  24. Pan, K. M., Baldwin, M., Nguyen, J., Gasset, M., Serban, A., Groth, D., Mehlhorn, I., Huang, Z., Fletterick, R. J., Cohen, F. E. & Prusiner, S. B. ( 1993; ). Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins. Proceedings of the National Academy of Sciences, USA 90, 10962-10966.[CrossRef]
    [Google Scholar]
  25. Parchi, P., Capellari, S., Chen, S. G., Petersen, R. B., Gambetti, P., Kopp, N., Brown, P., Kitamoto, T., Tateishi, J., Giese, A. & Kretzschmar, H. ( 1997; ). Typing prion isoforms. Nature 386, 232-234.[CrossRef]
    [Google Scholar]
  26. Pergami, P., Jaffe, H. & Safar, J. ( 1996; ). Semipreparative chromatographic method to purify the normal cellular isoform of the prion protein in nondenatured form. Analytical Biochemistry 236, 63-73.[CrossRef]
    [Google Scholar]
  27. Prusiner, S. B. & DeArmond, S. J. ( 1994; ). Prion diseases and neurodegeneration. Annual Review of Neuroscience 17, 311-339.[CrossRef]
    [Google Scholar]
  28. Riek, R., Hornemann, S., Wider, G., Billeter, M., Glockshuber, R. & Wuthrich, K. ( 1996; ). NMR structure of the mouse prion protein domain PrP(121–321). Nature 382, 180-182.[CrossRef]
    [Google Scholar]
  29. Safar, J., Roller, P. P., Gajdusek, D. C. & Gibbs, C. J.Jr ( 1993; ). Conformational transitions, dissociation, and unfolding of scrapie amyloid (prion) protein. Journal of Biological Chemistry 268, 20276-20284.
    [Google Scholar]
  30. Safar, J., Wille, H., Itri, V., Groth, D., Serban, H., Torchia, M., Cohen, F. E. & Prusiner, S. B. ( 1998; ). Eight prion strains have PrP(Sc) molecules with different conformations. Nature Medicine 4, 1157-1165.[CrossRef]
    [Google Scholar]
  31. Somerville, R. A. ( 1999; ). Host and transmissible spongiform encephalopathy agent strain control glycosylation of PrP. Journal of General Virology 80, 1865-1872.
    [Google Scholar]
  32. Somerville, R. A., Chong, A., Mulqueen, O. U., Birkett, C. R., Wood, S. C. & Hope, J. ( 1997; ). Biochemical typing of scrapie strains. Nature 386, 564.[CrossRef]
    [Google Scholar]
  33. Wadsworth, J. D. F., Hill, A. F., Joiner, S., Jackson, G. S., Clarke, A. R. & Collinge, J. ( 1999; ). Strain specific prion conformation determined by metal ions. Nature Cell Biology 1, 55-59.[CrossRef]
    [Google Scholar]
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