1887

Abstract

Both infectivity and TSE-specific amyloid protein (also referred to as protease resistant- or prion protein, PrP) are pathognomonic markers for transmissible spongiform encephalopathies (TSE). This paper presents a new densitometric method for the quantification of TSE-specific amyloid protein and its application to studying the pathogenesis of scrapie in Syrian hamsters after infection with scrapie strain 263K. A first study established a close correlation between infectivity and TSE-specific amyloid protein with a doubling time of 2–2.6 days in the brain and cervical spinal cord for both markers. The ratio of infectivity and TSE-specific unit during the course of infection. A subsequent study addressed the temporal-spatial spread of infection in the central nervous system by tracing the accumulation of the pathological protein. The pathogenetic process was first detected in the spinal cord between vertebrae T4 and T9, and then showed an anterograde and retrograde spread with a rate of 0.8–1⊙0 mm/day. There were also some indications for a possible alternative route of spread of infection from the periphery to the brain, other than via the spinal cord. Involvement of the spleen did not appear essential for the early pathogenesis in hamsters orally infected with the 263K strain of scrapie.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-77-8-1925
1996-08-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/jgv/77/8/JV0770081925.html?itemId=/content/journal/jgv/10.1099/0022-1317-77-8-1925&mimeType=html&fmt=ahah

References

  1. Barry R. A., Kent S. B., McKinley M. P., Meyer R. K., DeArmond S. J., Hood L. E., Prusiner S. B. 1986; Scrapie and cellular prion proteins share polypeptide epitopes. Journal of Infectious Diseases 153:848–854
    [Google Scholar]
  2. Basler K., Oesch B., Scott M., Westaway D., Waelchli M., Groth D. F., McKinley M. P., Prusiner S. B., Weissmann C. 1986; Scrapie and cellular PrP isoforms are encoded by the same chromosomal gene. Cell 46:417–428
    [Google Scholar]
  3. Beekes M., Baldauf E., CaBens S., Diringer H., Keyes P., Scott A. C., Wells G. A. H., Brown P., Gibbs C. J. Jr, Gajdusek D. C. 1995; Western blot mapping of disease-specific amyloid in various animal species and humans with transmissible spongiform encephalopathies using a high-yield purification method. Journal of General Virology 76:2567–2576
    [Google Scholar]
  4. Bendheim P. E., Potempska A., Kascsak R. J., Bolton D. C. 1988; Purification and partial characterization of the normal cellular homologue of the scrapie agent protein. Journal of Infectious Diseases 158:1198–1208
    [Google Scholar]
  5. Bolton D. C., Bendheim P. E. 1988; A modified host protein model of scrapie. CIBA Foundation Symposium 135:164–181
    [Google Scholar]
  6. 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]
  7. Bolton D. C., Bendheim P. E., Marmorstein A. D., Potempska A. 1987; Isolation and structural studies of the intact scrapie agent protein. Archives of Biochemistry and Biophysics 258:579–590
    [Google Scholar]
  8. Bolton D. C., Rudelli R. D., Currie J. R., Bendheim P. E. 1991; Copurification of Sp33–37 and scrapie agent from hamster brain prior to detectable histopathology and clinical disease. Journal of General Virology 72:2905–2913
    [Google Scholar]
  9. Carp R. I., Kascsak R. J., Wisniewski H. M., Merz P. A., Rubenstein R., Bendheim P., Bolton D. 1989; The nature of the unconventional slow infection agents remains a puzzle. Alzheimer Disease and Associated Disorders 3:79–99
    [Google Scholar]
  10. Carp R. I., Callahan S. M., Patrick B. A., Mehta P. D. 1994; Interaction of scrapie agent and cells of the lymphoreticular system. Archives of Virology 136:255–268
    [Google Scholar]
  11. Clarke M. C., Kimberlin R. H. 1984; Pathogenesis of mouse scrapie: distribution of agent in the pulp and stroma of infected spleens. Veterinary Microbiology 9:215–225
    [Google Scholar]
  12. Czub M., Braig H. R., Diringer H. 1986a; 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 67:2005–2009
    [Google Scholar]
  13. Czub M., Braig H. R., Blode H., Diringer H. 1986b; The major protein of SAF is absent from spleen and thus not an essential part of the scrapie agent. Archives of Virology 91:383–386
    [Google Scholar]
  14. 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]
  15. Dickinson A. G., Outram G. W. 1988; Genetic aspects of unconventional virus infections: the basis of the virino hypothesis. CIBA Foundation Symposia 435:63–88
    [Google Scholar]
  16. 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]
  17. Diringer H., Beekes M., Oberdieck U. 1994; The nature of the scrapie agent: the virus theory. Annals of the New York Academy of Sciences 724:246–258
    [Google Scholar]
  18. Gabizon R., McKinley M. P., Prusiner S. B. 1987; Purified prion proteins and scrapie infectivity copartition into liposomes. Proceedings of the National Academy of Sciences, USA 84:4017–4021
    [Google Scholar]
  19. Gabizon R., McKinley M. P., Groth D., Prusiner S. B. 1988; Immunoaffinity purification and neutralization of scrapie prion infectivity. Proceedings of the National Academy of Sciences, USA 85:6617–6621
    [Google Scholar]
  20. Gajdusek D. C. 1990; Subacute spongiform encephalopathies: transmissible cerebral amyloidoses caused by unconventional viruses. In Virology pp 2289–2324 Edited by Fields B. N., Knipe D. M., Chanock R. M. New York: Raven Press;
    [Google Scholar]
  21. Jendroska K., Heinzel F. P., Torchia M., Stowring L., Kretzschmar H. A., Kon A., Stern A., Prusiner S. B., DeArmond S. J. 1991; Proteinase-resistant prion protein accumulation in Syrian hamster brain correlates with regional pathology and scrapie infectivity. Neurology 41:1482–1490
    [Google Scholar]
  22. Kimberlin R. H., Walker C. 1977; Characteristics of a short incubation model of scrapie in the golden hamster. Journal of General Virology 34:295–304
    [Google Scholar]
  23. 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]
  24. Kimberlin R. H., Walker C. A. 1980; Pathogenesis of mouse scrapie: evidence for neural spread of infection to the CNS. Journal of General Virology 51:183–187
    [Google Scholar]
  25. Kimberlin R. H., Walker C. A. 1982; Pathogenesis of mouse scrapie: patterns of agent replication in different parts of the CNS following intraperitoneal infection. Journal of the Royal Society of Medicine 75:618–624
    [Google Scholar]
  26. Kimberlin R. H., Walker C. A. 1983; Invasion of the CNS by scrapie agent and its spread to different parts of the brain. In Virus Non-Convenlionels et Affections du Systeme Nerveaux Central pp 17–33 Edited by Court L. A., Cathala F. Paris: Masson;
    [Google Scholar]
  27. Kimberlin R. H., Walker C. A. 1986; Pathogenesis of scrapie (strain 263K) in hamsters infected intracerebrally, intraperitoneally or intraocularly. Journal of General Virology 67:255–263
    [Google Scholar]
  28. Kimberlin R. H., Walker C. A. 1989; Pathogenesis of scrapie in mice after intragastric infection. Virus Research 12:213–220
    [Google Scholar]
  29. Kimberlin R. H., Hall S. M., Walker C. A. 1983a; Pathogenesis of mouse scrapie. Evidence for direct neural spread of infection to the CNS after injection of sciatic nerve. Journal of the Neurological Sciences 61:315–325
    [Google Scholar]
  30. Kimberlin R. H., Field H. J., Walker C. A. 1983b; Pathogenesis of mouse scrapie: evidence for spread of infection from central to peripheral nervous system. Journal of General Virology 64:713–716
    [Google Scholar]
  31. 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]
  32. Manuelidis L., Murdoch G., Manuelidis E. E. 1988; Potential involvement of retroviral elements in human dementias. CIBA Foundation Symposia 135:117–134
    [Google Scholar]
  33. Meyer R. K., McKinley M. P., Bowman K. A., Braunfeld 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]
  34. Muramoto T., Kitamoto T., Tateishi J., Goto I. 1993; Accumulation of abnormal prion protein in mice infected with Creutzfeldt-Jakob disease via intraperitoneal route: a sequential study. American Journal of Pathology 143:1470–1479
    [Google Scholar]
  35. Oberdieck U., Xi Y. G., Pocchiari M., Diringer H. 1994; Characterisation of antisera raised against species-specific peptide sequences from scrapie-associated fibril protein and their application for post-mortem immunodiagnosis of spongiform encephalopathies. Archives of Virology 136:99–110
    [Google Scholar]
  36. Oesch B., Westaway D., Waelchli M., McKinley M. P., Kent S. B., 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]
  37. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144
    [Google Scholar]
  38. Prusiner S. B. 1987; Prions and neurodegenerative diseases. New England Journal of Medicine 317:1571–1581
    [Google Scholar]
  39. Prusiner S. B. 1991; Molecular biology of prion diseases. Science 252:1515–1522
    [Google Scholar]
  40. Prusiner S. B., Groth D. F., Cochran S. P., Masiarz F. R., McKinley M. P., Martinez H. M. 1980; Molecular properties, partial purification and assay by incubation period measurements of the hamster scrapie agent. Biochemistry 19:4883–4891
    [Google Scholar]
  41. Prusiner S. B., Cochran S. P., Groth D. F., Downey D. E., Bowman K. A., Martinez H. M. 1982; Measurement of the scrapie agent using an incubation time interval assay. Annals of Neurology 11:353–358
    [Google Scholar]
  42. Prusiner S. B., Scott M., Foster D., Pan K. M., Groth D., Mirenda C., Torchia M., Yang S. L., Serban D., Carlson G. A., Hoope P. C., Westaway D., DeArmond S. I. 1990; Transgenetic studies implicate interactions between homologous PrP isoforms in scrapie prion replication. Cell 63:673–686
    [Google Scholar]
  43. 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]
  44. Rohwer R. G. 1991; The scrapie agent: 'a virus by any other name'. Current Topics in Microbiology and Immunology 172:195–232
    [Google Scholar]
  45. 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 protease-resistant proteins. Journal of Infectious Diseases 164:29–35
    [Google Scholar]
  46. Somerville R. A. 1994; Diagnosis and agent structure: a discussion. In Transmissible Spongiform Encephalopathies: Proceedings of a Consultation on BSE with the Scientific Veterinary Committee of the Commission of the European Communities, Brussels, J4—15 September 1993 (working document for the European Commission, ref.: F,. II.3 -JC/003), pp 443–449 Edited by Bradley R., Marchant B.
    [Google Scholar]
  47. van Keulen L. J. M., Schreuder B. E. C., Meloen R. H., Poelen-van den Berg M., Mooij-Harkes G., Vromans M. E. W., Langeveld J. P. M. 1995; Immunohistochemical detection and localization of prion protein in brain tissue of sheep with natural scrapie. Veterinary Pathology 32:299–308
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-77-8-1925
Loading
/content/journal/jgv/10.1099/0022-1317-77-8-1925
Loading

Data & Media loading...

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