1887

Abstract

It has previously been reported that disease-associated prion protein (PrP) derived from natural scrapie and from sheep infected experimentally with bovine spongiform encephalopathy (BSE) differed in respect of their immunohistochemical and immunoblotting properties. For BSE, however, these initial observations were restricted to orally challenged sheep of the ARQ/ARQ PrP genotype. Here, extended examinations were performed on 28 sheep that developed neurological signs after BSE experimental infection by one of three routes. Intracerebrally infected ARQ/ARQ sheep showed more widespread and abundant accumulations of PrP in tissues of the lymphoreticular system (LRS) than VRQ/VRQ animals, whereas no peripheral PrP was detected in ARR/ARR sheep. The intensity and dissemination of PrP accumulation in LRS tissues were less than those found previously in orally dosed sheep. AHQ/AHQ sheep challenged orally and ARQ/AHQ and ARQ/ARQ animals infected intravenously showed similar LRS-tissue PrP distributions and levels to those of ARQ/ARQ sheep infected intracerebrally. The patterns of intra- and extracellular immunoreactivity to different PrP antibodies in brain and LRS tissues and the immunoblotting characteristics of PrP from brain samples remained constant, irrespective of the route of inoculation and the PrP genotype, and were the same as described previously for ARQ/ARQ sheep dosed orally with BSE. These results suggest that the intracellular truncation of BSE PrP and the proteinase K cleavage site of BSE PrP are not altered by PrP genotype or by route of inoculation and that, therefore, screening tests based on these properties can be applied to identify potential sheep BSE cases occurring naturally.

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2005-03-01
2019-11-13
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References

  1. Andréoletti, O., Berthon, P., Marc, D., Sarradin, P., Grosclaude, J., van Keulen, L., Schelcher, F., Elsen, J.-M. & Lantier, F. ( 2000; ). Early accumulation of PrPSc in gut-associated lymphoid and nervous tissues of susceptible sheep from a Romanov flock with natural scrapie. J Gen Virol 81, 3115–3126.
    [Google Scholar]
  2. Andrews, N. J., Farrington, C. P., Ward, H. J. T., Cousens, S. N., Smith, P. G., Molesworth, A. M., Knight, R. S. G., Ironside, J. W. & Will, R. G. ( 2003; ). Deaths from variant Creutzfeldt-Jakob disease in the UK. Lancet 361, 751–752.[CrossRef]
    [Google Scholar]
  3. Baylis, M., Houston, F., Goldmann, W., Hunter, N. & McLean, A. R. ( 2000; ). The signature of scrapie: differences in the PrP genotype profile of scrapie-affected and scrapie-free UK sheep flocks. Proc R Soc Lond B Biol Sci 267, 2029–2035.[CrossRef]
    [Google Scholar]
  4. Butler, D. ( 1998; ). Doubts over ability to monitor risks of BSE spread to sheep. Nature 395, 6–7.[CrossRef]
    [Google Scholar]
  5. 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.[CrossRef]
    [Google Scholar]
  6. Foster, J. D., Hope, J. & Fraser, H. ( 1993; ). Transmission of bovine spongiform encephalopathy to sheep and goats. Vet Rec 133, 339–341.[CrossRef]
    [Google Scholar]
  7. Foster, J. D., Parnham, D., Chong, A., Goldmann, W. & Hunter, N. ( 2001a; ). Clinical signs, histopathology and genetics of experimental transmission of BSE and natural scrapie to sheep and goats. Vet Rec 148, 165–171.[CrossRef]
    [Google Scholar]
  8. Foster, J. D., Parnham, D. W., Hunter, N. & Bruce, M. ( 2001b; ). Distribution of the prion protein in sheep terminally affected with BSE following experimental oral transmission. J Gen Virol 82, 2319–2326.
    [Google Scholar]
  9. Geysen, H. M., Meloen, R. H. & Barteling, S. J. ( 1984; ). Use of peptide synthesis to probe viral antigens for epitopes to a resolution of a single amino acid. Proc Natl Acad Sci U S A 81, 3998–4002.[CrossRef]
    [Google Scholar]
  10. 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.[CrossRef]
    [Google Scholar]
  11. González, L., Martin, S. & Jeffrey, M. ( 2003; ). Distinct profiles of PrPd immunoreactivity in the brain of scrapie- and BSE-infected sheep: implications on differential cell targeting and PrP processing. J Gen Virol 84, 1339–1350.[CrossRef]
    [Google Scholar]
  12. González, L., Martin, S., Houston, F. E., Hunter, N., Reid, H. W., Bellworthy, S. J. & Jeffrey, M. ( 2005; ). Phenotype of disease-associated PrP accumulation in the brain of bovine spongiform encephalopathy experimentally infected sheep. J Gen Virol 86, 827–838.[CrossRef]
    [Google Scholar]
  13. Heggebø, R., Press, C. McL., Gunnes, G., González, L. & Jeffrey, M. ( 2002; ). Distribution and accumulation of PrP in gut-associated and peripheral lymphoid tissue of scrapie-affected Suffolk sheep. J Gen Virol 83, 479–489.
    [Google Scholar]
  14. 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 J 5, 2591–2597.
    [Google Scholar]
  15. Hope, J., Multhaup, G., Reekie, L. J. D., Kimberlin, R. H. & Beyreuther, K. ( 1988; ). Molecular pathology of scrapie-associated fibril protein (PrP) in mouse brain affected by the ME7 strain of scrapie. Eur J Biochem 172, 271–277.[CrossRef]
    [Google Scholar]
  16. Houston, F., Goldmann, W., Chong, A., Jeffrey, M., González, L., Foster, J., Parnham, D. & Hunter, N. ( 2003; ). BSE in sheep bred for resistance to infection. Nature 423, 498.[CrossRef]
    [Google Scholar]
  17. Hunter, N., Foster, J., Chong, A., McCutcheon, S., Parnham, D., Eaton, S., MacKenzie, C. & Houston, F. ( 2002; ). Transmission of prion diseases by blood transfusion. J Gen Virol 83, 2897–2905.
    [Google Scholar]
  18. Jeffrey, M., Goodsir, C. M., Bruce, M. E., McBride, P. A. & Farquhar, C. ( 1994; ). Morphogenesis of amyloid plaques in 87V murine scrapie. Neuropathol Appl Neurobiol 20, 535–542.[CrossRef]
    [Google Scholar]
  19. Jeffrey, M., McGovern, G., Goodsir, C. M., Brown, K. L. & Bruce, M. E. ( 2000; ). Sites of prion protein accumulation in scrapie-infected mouse spleen revealed by immuno-electron microscopy. J Pathol 191, 323–332.[CrossRef]
    [Google Scholar]
  20. Jeffrey, M., Martin, S., González, L., Ryder, S. J., Bellworthy, S. J. & Jackman, R. ( 2001a; ). Differential diagnosis of infections with the bovine spongiform encephalopathy (BSE) and scrapie agents in sheep. J Comp Pathol 125, 271–284.[CrossRef]
    [Google Scholar]
  21. Jeffrey, M., Martin, S., Thomson, J. R., Dingwall, W. S., Begara-McGorum, I. & González, L. ( 2001b; ). Onset and distribution of tissue PrP accumulation in scrapie-affected Suffolk sheep as demonstrated by sequential necropsies and tonsillar biopsies. J Comp Pathol 125, 48–57.[CrossRef]
    [Google Scholar]
  22. Jeffrey, M., Ryder, S., Martin, S., Hawkins, S. A. C., Terry, L., Berthelin-Baker, C. & Bellworthy, S. J. ( 2001c; ). Oral inoculation of sheep with the agent of bovine spongiform encephalopathy (BSE). 1. Onset and distribution of disease-specific PrP accumulation in brain and viscera. J Comp Pathol 124, 280–289.[CrossRef]
    [Google Scholar]
  23. Jeffrey, M., Martin, S. & González, L. ( 2003; ). Cell-associated variants of disease-specific prion protein immunolabelling are found in different sources of sheep transmissible spongiform encephalopathy. J Gen Virol 84, 1033–1046.[CrossRef]
    [Google Scholar]
  24. Lezmi, S., Martin, S., Simon, S., Comoy, E., Bencsik, A., Deslys, J.-P., Grassi, J., Jeffrey, M. & Baron, T. ( 2004; ). Comparative molecular analysis of the abnormal prion protein in field scrapie cases and experimental bovine spongiform encephalopathy in sheep by use of Western blotting and immunohistochemical methods. J Virol 78, 3654–3662.[CrossRef]
    [Google Scholar]
  25. Prusiner, S. B. ( 1999; ). An introduction to prion biology and diseases. In Prion Biology and Diseases, pp. 1–66. Edited by S. B. Prusiner. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  26. Stack, M., Chaplin, M. & Clark, J. ( 2002; ). Differentiation of prion protein glycoforms from naturally occurring sheep scrapie, sheep-passaged scrapie strains (CH1641 and SSBP1), bovine spongiform encephalopathy (BSE) cases and Romney and Cheviot breed sheep experimentally inoculated with BSE using two monoclonal antibodies. Acta Neuropathol (Berl) 104, 279–286.
    [Google Scholar]
  27. Thuring, C. M. A., Erkens, J. H. F., Jacobs, J. G. & 8 other authors ( 2004; ). Discrimination between scrapie and bovine spongiform encephalopathy in sheep by molecular size, immunoreactivity, and glycoprofile of prion protein. J Clin Microbiol 42, 972–980.[CrossRef]
    [Google Scholar]
  28. 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]
  29. Van Keulen, L. J. M., Schreuder, B. E. C., Vromans, M. E. W., Langeveld, J. P. M. & Smits, M. A. ( 2000; ). Pathogenesis of natural scrapie in sheep. Arch Virol Suppl 16, 57–71.
    [Google Scholar]
  30. Van Keulen, L. J. M., Vromans, M. E. W. & van Zijderveld, F. G. ( 2002; ). Early and late pathogenesis of natural scrapie infection in sheep. APMIS 110, 23–32.[CrossRef]
    [Google Scholar]
  31. Wells, G. A. H., Hawkins, S. A. C., Green, R. B., Austin, A. R., Dexter, I., Spencer, Y. I., Chaplin, M. J., Stack, M. J. & Dawson, M. ( 1998; ). Preliminary observations on the pathogenesis of experimental bovine spongiform encephalopathy (BSE): an update. Vet Rec 142, 103–106.[CrossRef]
    [Google Scholar]
  32. Wilesmith, J. W., Wells, G. A. H., Ryan, J. B. M., Gavier-Widen, D. & Simmons, M. M. ( 1997; ). A cohort study to examine maternally-associated risk factors for bovine spongiform encephalopathy. Vet Rec 141, 239–243.[CrossRef]
    [Google Scholar]
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