1887

Abstract

Bovine spongiform encephalopathy (BSE) is acquired orally and the mechanisms involved in the absorption and transportation of infectivity across the gut wall are therefore critical. Isolated gut loops were created in lambs, massaged to remove intestinal contents (flushed) or left non-flushed, inoculated with cattle BSE homogenate and excised at different time-points. Gut loops were examined by immunohistochemistry (IHC) for disease-associated prion protein (PrP), and the contents were analysed by Western blotting (WB) to determine the degradation rate of protease-resistant PrP (PrP). The contents of scrapie-inoculated gut loops from a previous experiment were analysed by WB, and these digestion results were compared with those of an experiment on the same transmissible spongiform encephalopathy homogenates. BSE-inoculum-derived PrP was detected by IHC in the gut lumen between 15 min and 3.5 h. It was found in the intestinal lymphatic system from 30 min onwards and was present at the highest frequency at 120 min post-inoculation. degradation of PrP in the BSE inoculum had a significantly (=0.006) different pattern compared with scrapie-derived PrP, with the BSE PrP degrading more rapidly. However, the overall amount of degradation became similar by 120 min post-challenge. The results of the digestion experiments showed a similar pattern, although the magnitude of PrP degradation was less than in the environment where absorption could also take place. BSE-derived PrP is less protease resistant than scrapie PrP over a short time-course and the disappearance of detectable PrP from the gut lumen results from both absorption and digestion by intestinal contents.

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2010-12-01
2024-04-25
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References

  1. Ano, Y., Nakayama, H., Sakai, Y., Sakudo, A., Endo, M., Ebisu, S., Li, J., Uetsuka, K., Manabe, N. & Onodera, T.(2008). Incorporation of beta-amyloid protein through the bovine ileal epithelium before and after weaning: model for orally transmitted amyloidoses. Microbiol Immunol 52, 429–434.[CrossRef] [Google Scholar]
  2. Beekes, M. & McBride, P. A.(2000). Early accumulation of pathological PrP in the enteric nervous system and gut-associated lymphoid tissue of hamsters orally infected with scrapie. Neurosci Lett 278, 181–184.[CrossRef] [Google Scholar]
  3. Beekes, M. & McBride, P. A.(2007). The spread of prions through the body in naturally acquired transmissible spongiform encephalopathies. FEBS J 274, 588–605.[CrossRef] [Google Scholar]
  4. Bergström, A.-L., Jensen, T. K., Heegaard, P. M. H., Cordes, H., Hansen, V. B., Laursen, H. & Lind, P.(2006). Short-term study of the uptake of PrPSc by the Peyer's patches in hamsters after oral exposure to scrapie. J Comp Pathol 134, 126–133.[CrossRef] [Google Scholar]
  5. Bruce, M. E., Will, R. G., Ironside, J. W., McConnell, I., Drummond, D., Suttie, A., McCardle, L., Chree, A., Hope, J. & other authors(1997). Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389, 498–501.[CrossRef] [Google Scholar]
  6. Collinge, J.(2001). Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 24, 519–550.[CrossRef] [Google Scholar]
  7. Collins, S. J., Lawson, V. A. & Masters, C. L.(2004). Transmissible spongiform encephalopathies. Lancet 363, 51–61.[CrossRef] [Google Scholar]
  8. Flechsig, E., Hegyi, I., Enari, M., Schwarz, P., Collinge, J. & Weissmann, C.(2001). Transmission of scrapie by steel-surface-bound prions. Mol Med 7, 679–684. [Google Scholar]
  9. Gavier-Widén, D., Stack, M. J., Baron, T., Balachandran, A. & Simmons, M.(2005). Diagnosis of transmissible spongiform encephalopathies in animals: a review. J Vet Diagn Invest 17, 509–527.[CrossRef] [Google Scholar]
  10. Goldmann, W.(2008). PrP genetics in ruminant transmissible spongiform encephalopathies. Vet Res 39, 30.[CrossRef] [Google Scholar]
  11. 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]
  12. Hoinville, L. J.(1996). A review of the epidemiology of scrapie in sheep. Rev Sci Tech 15, 827–852. [Google Scholar]
  13. Jeffrey, M., Ryder, S., Martin, S., Hawkins, S. A. C., Terry, L., Berthelin-Baker, C. & Bellworthy, S. J.(2001). 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]
  14. Jeffrey, M., González, L., Espenes, A., Press, C. M., Martin, S., Chaplin, M., Davis, L., Landsverk, T., MacAldowie, C. & other authors(2006). Transportation of prion protein across the intestinal mucosa of scrapie-susceptible and scrapie-resistant sheep. J Pathol 209, 4–14.[CrossRef] [Google Scholar]
  15. Johnson, C. J., Phillips, K. E., Schramm, P. T., McKenzie, D., Aiken, J. M. & Pedersen, J. A.(2006). Prions adhere to soil minerals and remain infectious. PLoS Pathog 2, e32.[CrossRef] [Google Scholar]
  16. Kimberlin, R. H. & Wilesmith, J. W.(1994). Bovine spongiform encephalopathy. Epidemiology, low dose exposure and risks. Ann N Y Acad Sci 724, 210–220.[CrossRef] [Google Scholar]
  17. Kirkwood, J. K. & Cunningham, A. A.(1994). Epidemiologic observations on spongiform encephalopathies in captive wild animals in the British Isles. Vet Rec 135, 296–303.[CrossRef] [Google Scholar]
  18. Krüger, D., Thomzig, A., Lenz, G., Kampf, K., McBride, P. & Beekes, M.(2009). Faecal shedding, alimentary clearance and intestinal spread of prions in hamsters fed with scrapie. Vet Res 40, 4.[CrossRef] [Google Scholar]
  19. Kuczius, T. & Groschup, M. H.(1999). Differences in proteinase K resistance and neuronal deposition of abnormal prion proteins characterize bovine spongiform encephalopathy (BSE) and scrapie strains. Mol Med 5, 406–418. [Google Scholar]
  20. Manson, J. C., Cancellotti, E., Hart, P., Bishop, M. T. & Barron, R. M.(2006). The transmissible spongiform encephalopathies: emerging and declining epidemics. Biochem Soc Trans 34, 1155–1158.[CrossRef] [Google Scholar]
  21. M'Gowan, J. P.(1914).Investigation into the Disease of Sheep Called ‘Scrapie’. Edinburgh. : William Blackwood & Sons. [Google Scholar]
  22. Nicholson, E. M., Richt, J. A., Rasmussen, M. A., Hamir, A. N., Lebepe-Mazur, S. & Horst, R. L.(2007). Exposure of sheep scrapie brain homogenate to rumen-simulating conditions does not result in a reduction of PrPSc levels. Lett Appl Microbiol 44, 631–636.[CrossRef] [Google Scholar]
  23. Press, C. M., Heggebø, R. & Espenes, A.(2004). Involvement of gut-associated lymphoid tissue of ruminants in the spread of transmissible spongiform encephalopathies. Adv Drug Deliv Rev 56, 885–899.[CrossRef] [Google Scholar]
  24. Prusiner, S. B.(1998). Prions. Proc Natl Acad Sci U S A 95, 13363–13383.[CrossRef] [Google Scholar]
  25. Scherbel, C., Pichner, R., Groschup, M. H., Mueller-Hellwig, S., Scherer, S., Dietrich, R., Maertlbauer, E. & Gareis, M.(2006). Degradation of scrapie associated prion protein (PrPSc) by the gastrointestinal microbiota of cattle. Vet Res 37, 695–703.[CrossRef] [Google Scholar]
  26. Scherbel, C., Pichner, R., Groschup, M. H., Mueller-Hellwig, S., Scherer, S., Dietrich, R., Maertlbauer, E. & Gareis, M.(2007). Infectivity of scrapie prion protein (PrPSc) following in vitro digestion with bovine gastrointestinal microbiota. Zoonoses Public Health 54, 185–190.[CrossRef] [Google Scholar]
  27. Terry, L. A., Marsh, S., Ryder, S. J., Hawkins, S. A. C., Wells, G. A. H. & Spencer, Y. I.(2003). Detection of disease-specific PrP in the distal ileum of cattle exposed orally to the agent of bovine spongiform encephalopathy. Vet Rec 152, 387–392.[CrossRef] [Google Scholar]
  28. Wells, G. A. H.(2003). Pathogenesis of BSE. Vet Res Commun 27, 25–28.[CrossRef] [Google Scholar]
  29. Will, R. G.(2003). Acquired prion disease: iatrogenic CJD, variant CJD, kuru. Br Med Bull 66, 255–265.[CrossRef] [Google Scholar]
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