1887

Abstract

Previous studies have shown that the patterns of disease-specific prion protein (PrP) accumulation in the brain (the ‘PrP profile’) of scrapie-affected sheep are mainly influenced by the source of scrapie agent. We have now extended those studies to investigate the effect of different PrP antibodies on the PrP profile of scrapie- and bovine spongiform encephalopathy (BSE)-affected sheep. Immunohistochemical examination of brains of 20 sheep was performed with four different PrP antibodies (P4, 521.7, 505.2 and R486), and the animals were allocated to four groups of five sheep each depending on the transmissible spongiform encephalopathy (TSE) agent source (two natural scrapie sources, SSBP/1 and BSE). Although the PrP profiles depended on the antibody used, the four TSE sources could always be differentiated. Natural Suffolk scrapie showed the highest levels of glia-associated PrP, natural Welsh Mountain scrapie uniquely had consistent vascular PrP plaques, SSBP/1 produced the highest intracellular accumulations of PrP and BSE led to moderate accumulation of all PrP patterns except for vascular plaques. The variations in PrP profile between TSE sources appeared to be the result of variations in cell tropism and in PrP processing. These processing differences are possibly associated with changes in PrP conformation, and are manifest as differences in intracellular truncation and in release to the extracellular space of the abnormal protein. Moreover, variations in PrP conformation would appear to be also influenced by the cell type supporting infection, arguing that it is modulated by the interaction between the infectious agent and the host.

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2003-05-01
2024-03-29
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References

  1. Begara-McGorum I., González L., Simmons M., Hunter N., Houston F., Jeffrey M. 2002; Vacuolar lesion profile in sheep scrapie: factors influencing its variation and relationship to disease-specific PrP accumulation. J Comp Pathol 127:59–68
    [Google Scholar]
  2. Bessen R. A., Marsh R. F. 1994; Distinct PrP properties suggest the molecular basis of strain variation in transmissible mink encephalopathy. J Virol 68:7859–7868
    [Google Scholar]
  3. Bruce M. E. 1993; Scrapie strain variation and mutation. Br Med Bull 49:822–838
    [Google Scholar]
  4. 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. J Gen Virol 72:595–603
    [Google Scholar]
  5. Bruce M. E., Chree A., McConnell I., Foster J., Pearson G., Fraser H. 1994; Transmission of bovine spongiform encephalopathy and scrapie to mice: strain variation and the species barrier. Philos Trans R Soc Lond Ser B Biol Sci 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. DeArmond S. J., Sánchez H., Yehiely F. 12 other authors 1997; Selective neuronal targeting in prion disease. Neuron 19:1337–1348
    [Google Scholar]
  8. DeArmond S. J., Qiu Y., Sánchez H., Spilman P. R., Ninchak-Casey A., Alonso D., Daggett V. 1999; PrPc glycoform heterogeneity as a function of brain region: implications for selective targeting of neurons by prion strains. J Neuropathol Exp Neurol 58:1000–1009
    [Google Scholar]
  9. Díez M., DeArmond S. J., Groth D., Prusiner S. B., Hökfelt T. 2001; Decreased MK-801 binding in discrete hippocampal regions of prion-infected mice. Neurobiol Dis 8:692–699
    [Google Scholar]
  10. Foster J. D., Hope J., Fraser H. 1993; Transmission of bovine spongiform encephalopathy to sheep and goats. Vet Rec 133:339–341
    [Google Scholar]
  11. Foster J. D., Wilson M., Hunter N. 1996; Immunolocalisation of the prion protein (PrP) in the brains of sheep with scrapie. Vet Rec 139:512–515
    [Google Scholar]
  12. Fraser H., Dickinson A. G. 1973; Scrapie in mice: agent strain differences in the distribution and intensity of grey matter vacuolation. J Comp Pathol 83:29–40
    [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. J Gen Virol 75:989–995
    [Google Scholar]
  14. González L., Martin S., Begara-McGorum I., Hunter N., Houston F., Simmons M., Jeffrey M. 2002; Effects of agent strain and host genotype on PrP accumulation in the brain of sheep naturally and experimentally affected with scrapie. J Comp Pathol 126:17–29
    [Google Scholar]
  15. Guentchev M., Hainfellner J. A., Trabattoni G. R., Budka H. 1997; Distribution of parvalbumin-immunoreactive neurons in brain correlates with hippocampal and temporal cortical pathology in Creutzfeldt–Jakob disease. J Neuropathol Exp Neurol 56:1119–1124
    [Google Scholar]
  16. Hardt M., Baron T., Groschup M. H. 2000; A comparative study of immuno-histochemical methods for detecting abnormal prion protein with monoclonal and polyclonal antibodies. J Comp Pathol 122:43–53
    [Google Scholar]
  17. Hill A. F., Sidle K. C., Joiner S., Keyes P., Martin T. C., Dawson M., Collinge J. 1998; Molecular screening of sheep for bovine spongiform encephalopathy. Neurosci Lett 255:159–162
    [Google Scholar]
  18. Hill A. F., Butterworth R. J., Joiner S. 12 other authors 1999; Investigation of variant Creutzfeldt–Jakob disease and other human prion diseases with tonsil biopsy samples. Lancet 353:183–189
    [Google Scholar]
  19. Hunter N. 1998; Scrapie. Mol Biotechnol 9:225–234
    [Google Scholar]
  20. Jeffrey M., Wells G. A. H., Bridges A. W. 1990; An immunohistochemical study of the topography and cellular localization of three neural proteins in the sheep nervous system. J Comp Pathol 103:23–35
    [Google Scholar]
  21. 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. Neurosci Lett 174:39–42
    [Google Scholar]
  22. Jeffrey M., Martin S., González L., Ryder S. J., Bellworthy S. J., Jackman R. 2001; Differential diagnosis of infections with the bovine spongiform encephalopathy (BSE) and scrapie agents in sheep. J Comp Pathol 125:271–284
    [Google Scholar]
  23. Jeffrey M., Martin S., González L. L. 2003; Cell-associated variants of disease-specific protein immunolabelling are found in different sources of sheep transmissible spongiform encephalopathy. J Gen Virol 84:1033–1046
    [Google Scholar]
  24. Kascsak R. J., Rubenstein R., Merz P. A., Carp R. I., Wisinewski H. M., Diringer H. 1985; Biochemical differences among scrapie-associated fibrils support the biological diversity of scrapie agents. J Gen Virol 66:1715–1722
    [Google Scholar]
  25. Kuczius T., Haist I., Groschup M. H. 1998; Molecular analysis of bovine spongiform encephalopathy and scrapie strain variation. J Infect Dis 178:639–699
    [Google Scholar]
  26. Miller J. M., Jenny A. L., Taylor W. D., Marsh R. F., Rubenstein R., Race R. E. 1993; Immunohistochemical detection of prion protein in sheep with scrapie. J Vet Diagn Invest 5:309–316
    [Google Scholar]
  27. Pan K., Baldwin M., Nguyen J. 8 other authors 1993; Conversion of α -helices into β -sheets features in the formation of the scrapie prion proteins. Proc Natl Acad Sci U S A 90:10962–10966
    [Google Scholar]
  28. 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. J Infect Dis 164:29–35
    [Google Scholar]
  29. Ryder S. J., Spencer Y. I., Bellerby P. J., March S. A. 2001; Immunohistochemical detection of PrP in the medulla oblongata of sheep: the spectrum of staining in normal and scrapie-affected sheep. Vet Rec 148:7–13
    [Google Scholar]
  30. Safar J., Wille H., Itrri V., Groth D., Serban H., Torchia M., Cohen F. E., Prusiner S. B. 1998; Eight prion strains have PrPsc molecules with different conformations. Nat Med 4:1157–1165
    [Google Scholar]
  31. Somerville R. A. 1999; Host and transmissible spongiform encephalopathy agent strain control glycosylation of PrP. J Gen Virol 80:1865–1872
    [Google Scholar]
  32. Somerville R. A., Chong A., Mulqueen O. U., Birkett C. R., Wood S. C. E. R., Hope J. 1997; Biochemical typing of scrapie strains. Nature 386:564
    [Google Scholar]
  33. Telling G. C., Parchi P., DeArmond S. J. 7 other authors 1996; Evidence for the conformation of the pathological isoform of the prion protein enciphering and propagating prion diversity. Science 274:2079–2082
    [Google Scholar]
  34. 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. Vet Pathol 32:299–308
    [Google Scholar]
  35. van Keulen L. J. M., Schreuder B. E. C., Meloen R. H., Mooij-Harkes G., Vromans M. E. W., Langeveld J. P. M. 1996; Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34:1228–1231
    [Google Scholar]
  36. Wood J. L. N., McGill I. S., Done S. H., Bradley R. 1997; Neuropathology of scrapie: a study of the distribution of brain lesions in 222 cases of natural scrapie in sheep, 1982–1991. Vet Rec 140:167–174
    [Google Scholar]
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