1887

Abstract

Infectivity within the central nervous system has been demonstrated by the transmission of bovine spongiform encephalopathy (BSE) from affected cattle to inbred laboratory mice. Sedimentable, protease-resistant PrP (PrP) has also been extracted from BSE-affected cattle brain. Both infectivity and PrP have been reported in the lymphoreticular tissues of sheep and mice clinically and preclinically affected with scrapie. Neither infectivity nor PrP has yet been detected in non-neural tissues of naturally occurring, clinical cases of BSE in cattle. We have used a murine model of BSE (301V isolate in VM/Dk mice) to investigate when and where PrP accumulates. PrP was detected both in brain and in extraneural sites prior to the onset of clinical symptoms. This murine BSE model differs, however, in four important aspects from our previously published findings for murine scrapie models: () PP was found relatively late into the incubation period; () after intracerebral inoculation, PrP was found in brain before it was found in other tissues; () no PrP was found in most of the spleens from clinically affected animals after intracerebral inoculation; and () even after intra-peritoneal infection, PrP was detected in brain first.

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1996-08-01
2024-04-25
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References

  1. Bolton D. C., Meyer R. K., Prusiner S. B. 1985; Scrapie PrP 27-30 is a sialoglycoprotein. ]ournal of Virology 53:596–606
    [Google Scholar]
  2. 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
    [Google Scholar]
  3. Bruce M. E., Chree A., McConnell I., Foster J., Pearson G., Fraser H. 1994a; Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Philosophical Transactions of the Royal Society of London B 343:405–411
    [Google Scholar]
  4. Bruce M. E., Chree A., McConnell I., Foster J., Pearson G., Fraser H. 1994b; Agent strain variation in BSE and scrapie. 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 189–204 Edited by Bradley R., Marchant B. European Commission
    [Google Scholar]
  5. Büeler H., Agussi A., Sailer A., Greiner R.-A., Autenried P., Aguet M., Weissmann C. 1993; Mice devoid of PrP are resistant to scrapie. Cell 73:1339–1347
    [Google Scholar]
  6. Carp R. I., Callahan S. M., Sersen E. A., Moretz R. C. 1984; Preclinical changes in weight of scrapie-infected mice as a function of scrapie agent–mouse strain combinations. Intervirology 21:61–69
    [Google Scholar]
  7. Czub M., Braig H. R., Diringer H. 1986; Pathogenesis of scrapie: study of the temporal development of clinical symptoms, of infectivity titre and scrapie-associated fibrils in the brains of hamsters infected intraperitoneally. Journal of General Virology 67:2005–2009
    [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 & General Genetics 112:73–79
    [Google Scholar]
  9. Dickinson A. G., Meikle V. M. H., Fraser H. 1968; Identification of a gene which controls the incubation period of some strains of scrapie agent in mice. Journal of Comparative Pathology 78:293–299
    [Google Scholar]
  10. Diringer H., Gelderblom H., Hilmert H., Ozel M., Edelbluth C., Kimberlin R. H. 1983; Scrapie infectivity, fibrils and low molecular weight protein. Nature 306:476–478
    [Google Scholar]
  11. Doi S., Ito M., Shinagawa M., Sato G., Isomura H., Goto H. 1988; Western blot detection of scrapie-associated fibril protein in tissues outside the central nervous system from preclinical scrapie-infected mice. Journal of General Virology 69:955–960
    [Google Scholar]
  12. 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]
  13. Farquhar C. F., Somerville R. A., Ritchie L. A. 1989; Post-mortem immunodiagnosis of scrapie and bovine spongiform encephalopathy. Journal of Virological Methods 24:215–222
    [Google Scholar]
  14. Farquhar C. F., Somerville R. A., McBride P., Bruce M. E., Hope J. 1990; PrP detection in peripheral organs of scrapie infected mice. In Abstracts of the VIIIth International Congress of Virology, Berlin26–31 August 1990 Abstract P28-013, p 284
    [Google Scholar]
  15. Farquhar C. F., Dornan J., Somerville R. A., Tunstall A. M., Hope J. 1994a; Effect of Sine genotype, agent isolate and route of infection on the accumulation of protease-resistant PrP in non-central nervous system tissues during the development of murine scrapie. Journal of General Virology 75:495–504
    [Google Scholar]
  16. Farquhar C. F., Somerville R. A., Dornan J., Armstrong D., Birkett C., Hope J. 1994b; A review of the detection of PrPSc . 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 301–313 Edited by Bradley R., Marchant B. European Commission
    [Google Scholar]
  17. Fraser H., Dickinson A. G. 1970; Pathogenesis of scrapie in the mouse: the role of the spleen. Nature 226:462–463
    [Google Scholar]
  18. Fraser H., Dickinson A. G. 1978; Studies of the lymphoreticular system in the pathogenesis of scrapie: the role of the spleen and thymus. Journal of Comparative Pathology 88:563–573
    [Google Scholar]
  19. Fraser H., Foster J. D. 1994; Transmission to mice, sheep and goats and bioassay of bovine tissues. 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 145–159 Edited by Bradley R., Marchant B. European Commission
    [Google Scholar]
  20. Fraser H., McConnell I., Wells G. A. H., Dawson M. 1988; Transmission of bovine spongiform encephalopathy to mice. Veterinary Record 123:472
    [Google Scholar]
  21. Fraser H., Bruce M. E., Chree A., McConnell I., Wells G. A. H. 1992; Transmission of bovine spongiform encephalopathy and scrapie in mice. Journal of General Virology 73:1891–1897
    [Google Scholar]
  22. 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]
  23. Hope J., Multhaup G., Reekie L. J. D., Kimberlin R. H., Beyreuther K. 1988a; Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie. European Journal of Biochemistry 172:271–277
    [Google Scholar]
  24. Hope J., Reekie L. J. D., Hunter N., Multhaup G., Beyreuther K., White H., Scott A. C., Stack M. J., Dawson M., Wells G. A. H. 1988b; Fibrils from brains of cows with new cattle disease contain scrapie-associated protein. Nature 336:390–392
    [Google Scholar]
  25. Ikegami M., Isomura H., Momotani E., Sasakli K., Muramatsu Y., Ishiguro N., Shinagawa M. 1991; Preclinical and clinical diagnosis of scrapie by detection of PrP protein in tissues of sheep. Veterinary Record 128:271–275
    [Google Scholar]
  26. Kimberlin R. H., Walker C. A. 1979; Pathogenesis of mouse scrapie: dynamics of agent replication in spleen, spinal cord and brain after infection by different routes. Journal of Comparative Pathology 89:551–562
    [Google Scholar]
  27. Kimberlin R. H., Walker C. A. 1988; Pathogenesis of scrapie in mice after intragastric infection. Virus Research 12:213–220
    [Google Scholar]
  28. 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]
  29. 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]
  30. Meyer R. K., McKinley M. P., Bowman K. A., Braunfield M. B., Barry R. A., Prusiner S. B. 1986; Separation and properties of cellular and scrapie prion proteins. Proceedings of the National Academy of Sciences, USA 83:2310–2314
    [Google Scholar]
  31. Middleton D. J., Barlow R. M. 1993; Failure to transmit bovine spongiform encephalopathy to mice by feeding them with extraneural tissues of affected cattle. Veterinary Record 132:545–547
    [Google Scholar]
  32. Millson G. C., Kimberlin R. H., Manning E. J., Collis S. C. 1979; Early distribution of radioactive liposomes and scrapie infectivity in mouse tissues following administration by different routes. Veterinary Microbiology 4:89–99
    [Google Scholar]
  33. Mohri S., Farquhar C. F., Somerville R. A., Jeffrey M., Foster J., Hope J. 1992; Immuno-detection of a disease specific PrP fraction in clinically affected scrapie sheep and BSE cattle. Veterinary Record 131:537–539
    [Google Scholar]
  34. Oesch B., Westaway D., Walchii M., McKinley M. P., Kent S. B. H., Aebersold R., Barry R. A., Tempst P., Teplow D. B., Hood L. E., Prusiner S. B., Weissmann C. 1985; A cellular gene encodes scrapie PrP 27-30 protein. Cell 40:735–746
    [Google Scholar]
  35. Onodera T., Ikeda T., Muramatsu Y., Shinagawa M. 1993; Isolation of scrapie agent from the placenta of sheep with natural scrapie in Japan. Microbiology and Immunology 37:311–316
    [Google Scholar]
  36. Outram G. W. 1972; Changes in the drinking and feeding habits of mice with experimental scrapie. Journal of Comparative Pathology 82:415–427
    [Google Scholar]
  37. Race R., Ernst D. 1992; Detection of a proteinase K-resistant prion protein and infectivity in mouse spleen by 2 weeks after scrapie agent inoculation. ]oumal of General Virology 73:3319–3323
    [Google Scholar]
  38. Race R., Ernst D., Jenny A., Taylor W., Sutton D., Caughey B. 1992; Diagnostic implications of detection of proteinase K-resistant protein in spleen, lymph nodes, and brain of sheep. American Journal of Veterinary Research 53:883–889
    [Google Scholar]
  39. Rubenstein R., Kascsak R. J., Merz P. A., Papini M. C., Carp R. I., Robakis N. K., Wisniewski H. M. 1986; Detection of scrapie-associated fibril (SAF) proteins using anti-SAF antibody in non-purified tissue preparations. Journal of General Virology 67:671–681
    [Google Scholar]
  40. Rubenstein R., Merz P. A., Kascsak R. J., Carp R. I., Scalici C. L., Sama C. L., Wisniewski H. M. 1987; Detection of scrapie-associated fibrils (SAF) and SAF proteins from scrapie-affected sheep. Journal of Infectious Diseases 156:35–42
    [Google Scholar]
  41. Rubenstein R., Merz P. A., Kascsak R. J., Scalici C. L., Papini M. C., Carp R. I., Kimberlin R. H. 1991; Scrapie-infected spleens: analysis of infectivity, scrapie-associated fibrils, and proteinase-resistant proteins. Journal of Infectious Diseases 164:29–35
    [Google Scholar]
  42. Shinagawa M., Munekata E., Doi S., Takahashi K., Goto H., Sato G. 1986; Immunoreactivity of a synthetic pentapeptide corresponding to the N-terminal region of the scrapie prion protein. Journal of General Virology 67:1745–1750
    [Google Scholar]
  43. Taylor D. M. 1994; Deactivation of BSE and scrapie agents: rendering and other U.K. studies. 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 205–223 Edited by Bradley R., Marchant B. European Commission
    [Google Scholar]
  44. Wells G. A. H., Hawkins S. A. C., Hadlow W. J., Spencer Y. I. 1992; The discovery of bovine spongiform encephalopathy and observations on the vacuolar changes. In Prion Diseases of Humans and Animals pp 256–274 Edited by Prusiner S. B., Collinge J., Powell J., Anderton B. London: Ellis Horwood;
    [Google Scholar]
  45. Wells G. A. H., Dawson M., Hawkins S. A. C., Green R. B., Dexter I., Francis M. E., Simmons M. M., Austin A. R., Horigan M. W. 1994; Infectivity in the ileum of cattle challenged orally with bovine spongiform encephalopathy. Veterinary Record 135:40–41
    [Google Scholar]
  46. Wilesmith J. W., Ryan J. B. M., Atkinson M. J. 1991; Bovine spongiform encephalopathy: epidemiological studies on the origin. Veterinary Record 128:199
    [Google Scholar]
  47. Zlotnik I. 1962; The pathology of scrapie: a comparative study of lesions in the brain of sheep and goats. Acta Neuropathologica Suppl 1:61–70
    [Google Scholar]
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