1887

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Volume 82, Issue 1

Partial dissociation of PrP deposition and vacuolation in the brains of scrapie and BSE experimentally affected goats Free

Abstract

The diagnosis of transmissible spongiform encephalopathies (TSEs) depends on the detection of vacuolation in brain sections taken from affected individuals and/or the identification of the disease-associated isoform of the PrP (prion) protein (PrP). During the course of an investigation, goats clinically affected following experimental infection with three different sources of TSE (SSBP/1, CH1641 and BSE) developed widespread vacuolar degeneration in the brain. With BSE, PrP was clearly recognized in affected goat brain by immunocytochemistry (icc) and Western blotting, but in contrast the experimental scrapie sources SSBP/1 and CH1641 showed almost no or very little PrP by icc. Western blot analysis of PrP from BSE-affected and SSBP/1-affected goat brain showed that the protein was present in brain affected by both TSE sources, but could not be used to determine how much protein was present. It became clear that PrP and vacuolation could be partially dissociated following challenge with two of the three TSE sources. Subtle differences in glycosylation patterns between BSE- and SSBP/1-associated PrP protein isoforms could also be recognized, although these experimentally generated results should not be regarded as a BSE/scrapie differential test. However, our study warns that the reliance on PrP determination by icc alone as a means by which to diagnose TSE infection may generate false negative results.

  • Received:
  • Accepted:
  • Published Online:
© Microbiology Society
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2001-01-01
2024-04-19
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References

  1. Allsop D., Ikeda S., Bruce M., Glenner G. G. 1988; Cerebrovascular amyloid in scrapie-affected sheep reacts with antibodies to prion protein. Neuroscience Letters 92:234–239
     [Google Scholar]
  2. Baron T. G. M., Madec J.-Y., Calvas 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]
  3. Bolton D. C., McKinley M. P., Prusiner S. B. 1982; Identification of a protein that purifies with the scrapie prion. Science 218:1309–1311
     [Google Scholar]
  4. Brown D. R., Schmidt B., Kretzschmar H. A. 1996; Role of microglia and host prion protein in neurotoxicity of prion protein fragment. Nature 380:345–347
     [Google Scholar]
  5. Bruce M., Chree A., McConnell I., Foster J., Pearson G., Fraser G. 1994; Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Philosophical Transactions of the Royal Society of London B Biological Sciences 343:405–411
     [Google Scholar]
  6. Collinge J., Sidle K. C. L., 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
     [Google Scholar]
  7. Dickinson A. G., Outram G. W., Taylor D. M., Foster J. D. 1989; Further evidence that scrapie agent has an independent genome. In Unconventional Virus Diseases of the Central Nervous System . pp 446–460 Edited by Court L. A., Dormont D., Brown P., Kingsbury D. T. Abbaye de Melleray,La Meillerange-de-Bretagne
  8. Foster J. D., Dickinson A. G. 1988; The unusual properties of CH1641: a sheep passaged isolate of scrapie. Veterinary Record 123:5–8
     [Google Scholar]
  9. Foster J. D., Hope J., Fraser H. 1993; Transmission of bovine spongiform encephalopathy to sheep and goats. Veterinary Record 133:339–341
     [Google Scholar]
  10. Foster J. D., Wilson M., Hunter N. 1996; Immunolocalisation of the prion protein (PrP) in the brains of sheep with scrapie. Veterinary Record 139:512–515
     [Google Scholar]
  11. Foster J., McKelvey W., Fraser H., Chong A., Ross A., Parnham D., Goldmann W., Hunter N. 1999; Experimentally induced bovine spongiform encephalopathy did not transmit via goat embryos. Journal of General Virology 80:517–524
     [Google Scholar]
  12. Fraser H., Bruce M. E., Chree A., McConnell I., Wells G. A. H. 1992; Transmission of bovine spongiform encephalopathy and scrapie to mice. Journal of General Virology 73:1891–1897
     [Google Scholar]
  13. Goldmann W., Hunter N., Smith G., Foster J., Hope J. 1994; PrP genotype and agent effects in scrapie: change in allelic interaction with different isolates of agent in sheep, a natural host of scrapie. Journal of General Virology 75:989–995
     [Google Scholar]
  14. Goldmann W., Martin T., Foster J., Hughes S., Smith G., Hughes K., Dawson M., Hunter N. 1996; Novel polymorphisms in the caprine PrP gene: a codon 142 mutation associated with scrapie incubation period. Journal of General Virology 77:2885–2891
     [Google Scholar]
  15. Goldmann W., Chong A., Foster J., Hope J., Hunter N. 1998; The shortest known prion protein gene allele occurs in goats, has only three octapeptide repeats and is non-pathogenic. Journal of General Virology 79:3173–3176
     [Google Scholar]
  16. Hope J., Morton L. J. D., Farquhar C. F., Multhaup G., Beyreuther K., Kimberlin R. H. 1986; The major polypeptide of scrapie-associated fibrils (SAF) has the same size, charge-distribution and N-terminal protein sequence as predicted for the normal brain protein (PrP). EMBO Journal 5:2591–2597
     [Google Scholar]
  17. 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]
  18. Hunter N., Foster J. D., Goldmann W., Stear M. J., Hope J., Bostock C. 1996; Natural scrapie in a closed flock of Cheviot sheep occurs only in specific PrP genotypes. Archives of Virology 141:809–824
     [Google Scholar]
  19. Jeffrey M., Goodsir C. M., Bruce M. E., McBride P. A., Fowler N., Scott J. R. 1994; Murine scrapie-infected neurons in vivo release excess prion protein into the extracellular space. Neuroscience Letters 174:39–42
     [Google Scholar]
  20. Langeveld J. P. M., Farquhar C. F., Pocchiari M., Birkett C., Bostock C., Meloen R. H. 1994; Antigenic sites of bovine prion protein. In BSE Update. Proceedings of a Consultation on BSE with the Scientific Veterinary Committee of the Commission of the European Communities, 14–15th September 1993, Brussels pp 315–321 Edited by Bradley R., Marchant B. Brussels: European Commission;
     [Google Scholar]
  21. McBride P. A., Bruce M. E., Fraser H. 1988; Immunostaining of scrapie cerebral amyloid plaques with antisera raised to scrapie-associated fibrils. Neuropathology and Applied Neurobiology 14:325–336
     [Google Scholar]
  22. McKinley M. P., Bolton D. C., Prusiner S. B. 1983; A protease-resistant protein is a structural component of the scrapie prion. Cell 35:57–62
     [Google Scholar]
  23. Miller J. M., Jenny A. L., Taylor W. D., Marsh R. F., Rubenstein R., Race R. E., Detweiler A. 1993; Immunohistochemical detection of prion protein in sheep with scrapie. Journal of Veterinary Diagnosis and Investigation 5:309–316
     [Google Scholar]
  24. Miller J. M., Jenny A. L., Taylor W. D., Race R. E., Ernst D. R., Katz J. B., Rubenstein R. 1994; Detection of prion protein in formalin-fixed brain by hydrated autoclaving immunohistochemistry for the diagnosis of scrapie in sheep. Journal of Veterinary Diagnosis and Investigation 6:366–368
     [Google Scholar]
  25. Prusiner S. B., Mackinley M. P., Bowman K., 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. Safar J., Wille H., Itri V., Groth D., Serban H., Torchia M., Cohen F. E., Prusiner S. B. 1998; Eight prion strains have PrPSc molecules with different conformations. Nature Medicine 4:1157–1165
     [Google Scholar]
  27. Schreuder B. E. C., van Keulen L. J. M., Vromans M. E. W., Langeveld J. P. M., Smits M. A. 1996; Pre-clinical test for prion diseases. Nature 381:363
     [Google Scholar]
  28. Sternberger L. A., Hardy P. H., Cuculis J. J., Meyer H. G. 1970; The unlabelled antibody–enzyme method of immunohistochemistry. Preparation of soluble antigen–antibody complex (horseradish peroxidase–antihorseradish peroxidase) and its use in the identification of spirochetes. Journal of Histochemical Cytochemistry 18:315–333
     [Google Scholar]
  29. van Keulen L. J. M., Schreuder B. E. C., Meloen R. H., Mooij-Harkes G., Poelen-van den Berg M., Vromans M. E. W., Langeveld J. 1995; Immunohistochemical detection and localization of prion protein in brain tissue in sheep with natural scrapie. Veterinary Pathology 32:299–308
     [Google Scholar]
  30. van Keulen L. J. M., Schreuder B. E. C., Meloen R. H., Mooij-Harkes G., Vromans M. E. W., Langeveld J. P. M. 1996; Immunohistological detection of prion protein in lymphoid tissues of sheep with natural scrapie. Journal of Clinical Microbiology 34:1228–1231
     [Google Scholar]
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Partial dissociation of PrPSc deposition and vacuolation in the brains of scrapie and BSE experimentally affected goats
J. Gen. Virol. 82, 267 (2001); https://doi.org/10.1099/0022-1317-82-1-267
/content/journal/jgv/10.1099/0022-1317-82-1-267
/content/journal/jgv/10.1099/0022-1317-82-1-267
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