1887

Abstract

The central molecular event in transmissible spongiform encephalopathies, such as scrapie in sheep, is the accumulation in tissues of an abnormal isoform of the cellular prion protein. A previous investigation of 26 sheep showed that the accumulation of PrP in brain correlated more with the genotype than with the severity of the clinical disease. Here, the ability of a sandwich ELISA to detect PrP distribution in the brain was demonstrated. Immunohistochemistry also strongly supported the hypothesis that the dorsal motor nucleus of the vagus nerve is the possible entry site in the brain for the scrapie agent. Remarkably, three asymptomatic (or possibly asymptomatic for scrapie) sheep carrying an allele known to be associated with clinical scrapie resistance (ARR), which were negative for the detection of PrP by Western blotting and immunohistochemistry, were positive for the presence of PrP by ELISA, raising the possibility of carriers resistant to the disease and possibly contributing to the persistence of scrapie in certain flocks.

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2004-11-01
2019-10-21
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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. Andréoletti, O., Lacroux, C., Chabert, A. & 8 other authors ( 2002; ). PrPSc accumulation in placentas of ewes exposed to natural scrapie: influence of foetal PrP genotype and effect on ewe-to-lamb transmission. J Gen Virol 83, 2607–2616.
    [Google Scholar]
  3. Begara-McGorum, I., Gonzalez, 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, 39–68.
    [Google Scholar]
  4. Belt, P. B. G. M., Muilheman, J. H., Schreuder, B. E. C., Ruitjer, J., Bos, D. E., Gielkens, A. L. J. & Smits, M. A. ( 1995; ). Identification of five allelic variants of the sheep PrP gene and their association with natural scrapie. J Gen Virol 75, 509–517.
    [Google Scholar]
  5. Bencsik, A., Lezmi, S. & Baron, T. ( 2001a; ). Autonomous nervous system innervation of lymphoid territories in spleen: a possible involvement of noradrenergic neurons for prion neuroinvasion in natural scrapie. J Neurovirol 7, 447–453.[CrossRef]
    [Google Scholar]
  6. Bencsik, A., Lezmi, S., Hunsmann, G. & Baron, T. ( 2001b; ). Close vicinity of PrP expressing cells (FDC) with noradrenergic fibers in healthy sheep spleen. Dev Immunol 8, 235–241.[CrossRef]
    [Google Scholar]
  7. Benestad, S., Sarradin, P., Thu, B., Schonheit, J., Tranulis, M. & Bratberg, B. ( 2003; ). Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec 153, 202–208.[CrossRef]
    [Google Scholar]
  8. Bennion, B. & Daggett, V. ( 2002; ). Protein conformation and diagnostic tests: the prion protein. Clin Chem 48, 2105–2114.
    [Google Scholar]
  9. Bossers, A., Schreuder, B. E. C., Muileman, I. H., Belt, P. B. G. & Smits, M. A. ( 1996; ). PrP genotype contributes to determining survival times of sheep with natural scrapie. J Gen Virol 77, 2669–2673.[CrossRef]
    [Google Scholar]
  10. Buschmann, A., Biacabe, A., Ziegler, U., Bencsik, A., Madec, J., Erhardt, G., Lühken, G., Baron, T. & Groschup, M. ( 2003; ). Atypical scrapie cases in Germany and France are identified by discrepant reaction patterns in BSE rapid tests. J Virol Methods 117, 27–36.
    [Google Scholar]
  11. Clouscard, C., Beaudry, P., Elsen, J.-M. & 7 other authors ( 1995; ). Different allelic effects of the codons 136 and 171 of the prion protein gene in sheep with natural scrapie. J Gen Virol 76, 2097–2101.[CrossRef]
    [Google Scholar]
  12. Collis, S. & Kimberlin, R. ( 1985; ). Long-term persistence of scrapie infection in mouse spleens in the absence of clinical disease. FEMS Microbiol 29, 111–114.[CrossRef]
    [Google Scholar]
  13. Crozet, C., Flamant, F., Bencsik, A., Aubert, D., Samarut, J. & Baron, T. ( 2001; ). Efficient transmission of two different sheep scrapie isolates transgenic mice expressing the ovine PrP gene. J Virol 75, 5328–5334.[CrossRef]
    [Google Scholar]
  14. Demart, S., Fournier, J. G., Creminon, C. & 7 other authors ( 1999; ). New insight into abnormal prion protein using monoclonal antibodies. Biochem Biophys Res Comm 265, 652–657.[CrossRef]
    [Google Scholar]
  15. Ersdal, C., Ulvund, M., Benestad, S. & Tranulis, M. ( 2003; ). Accumulation of pathogenic prion protein (PrPSc) in nervous and lymphoid tissues of sheep with subclinical scrapie. Vet Pathol 40, 164–174.[CrossRef]
    [Google Scholar]
  16. 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.[CrossRef]
    [Google Scholar]
  17. 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.[CrossRef]
    [Google Scholar]
  18. Gonzalez, 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]
  19. Hardt, M., Baron, T. & Groschup, M. H. ( 2000; ). A comparative study of immunohistochemical methods for detecting abnormal prion protein with monoclonal and polyclonal antibodies. J Comp Pathol 122, 43–53.[CrossRef]
    [Google Scholar]
  20. Heggebo, R., Press, C. M., Gunnes, G., Gonzalez, 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]
  21. Houston, F., Goldmann, W., Chong, A., Jeffrey, M., Gonzalez, L., Foster, J., Parnham, D. & Hunter, N. ( 2003; ). BSE in sheep bred for resistance to infection. Nature 423, 498.[CrossRef]
    [Google Scholar]
  22. Hunter, N. ( 1997; ). Molecular biology and genetics of scrapie in sheep. In The Genetics of Sheep, pp. 225–240. Edited by L. Piper & A. Ruvinsky. Wallingford, UK: CAB International.
  23. Hunter, N., Moore, L., Hosie, B. D., Dingwall, W. S. & Greig, A. ( 1997; ). Association between natural scrapie and PrP genotype in a flock of Suffolk sheep in Scotland. Vet Rec 140, 59–63.[CrossRef]
    [Google Scholar]
  24. Jeffrey, M., Begara-McGorum, I., Clark, S., Martin, S., Clark, J., Chaplin, M. & Gonzalez, L. ( 2002; ). Occurrence and distribution of infection-specific PrP in tissues of clinical scrapie cases and cull sheep from scrapie-affected farms in Shetland. J Comp Pathol 127, 264–273.[CrossRef]
    [Google Scholar]
  25. Krasemann, S., Groschup, M. H., Harmeyer, S., Hunsmann, G. & Bodemer, W. ( 1996; ). Generation of monoclonal antibodies against human prion proteins in PrP0/0 mice. Mol Med 2, 725–734.
    [Google Scholar]
  26. Krasemann, S., Jürgens, T. & Bodemer, W. ( 1999; ). Generation of monoclonal antibodies against prion proteins with an unconventional nucleic acid-based immunization strategy. J Biotechnol 73, 119–129.[CrossRef]
    [Google Scholar]
  27. Lasmézas, C. I., Deslys, J. P., Demaimay, R., Adjou, K. T., Hauw, J. J. & Dormont, D. ( 1996; ). Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy. J Gen Virol 77, 1601–1609.[CrossRef]
    [Google Scholar]
  28. Lasmézas, C. I., Deslys, J.-P., Robain, O. & 7 other authors ( 1997; ). Transmission of the BSE agent to mice in the absence of detectable abnormal prion protein. Science 275, 402–405.[CrossRef]
    [Google Scholar]
  29. Lezmi, S., Bencsik, A. & Baron, T. ( 2001; ). CNA 42 monoclonal antibody identifies FDC as PrPSc accumulating cells in the spleen of scrapie affected sheep. Vet Immunol Immunopathol 82, 1–8.[CrossRef]
    [Google Scholar]
  30. Ligios, C., Jeffrey, M., Ryder, S. J., Bellworthy, S. J. & Simmons, M. M. ( 2002; ). Distinction of scrapie phenotypes in sheep by lesion profiling. J Comp Pathol 127, 45–57.[CrossRef]
    [Google Scholar]
  31. Madec, J.-Y., Groschup, M. H., Calavas, D., Junghans, F. & Baron, T. ( 2000; ). Protease-resistant prion protein in brain and lymphoid organs of sheep within a naturally scrapie-infected flock. Microb Pathog 28, 353–362.[CrossRef]
    [Google Scholar]
  32. Manuelidis, L., Fritch, W. & Xi, Y. G. ( 1997; ). Evolution of a strain of CJD that induces BSE-like plaques. Science 277, 94–98.[CrossRef]
    [Google Scholar]
  33. 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.[CrossRef]
    [Google Scholar]
  34. Onodera, T., Ikeda, T., Muramatsu, Y. & Shinagawa, M. ( 1993; ). Isolation of scrapie agent from the placenta of sheep with natural scrapie in Japan. Microbiol Immunol 37, 311–316.[CrossRef]
    [Google Scholar]
  35. Pattison, I. H. ( 1988; ). Fifty years with scrapie: a personal reminiscence. Vet Rec 123, 661–666.
    [Google Scholar]
  36. Prusiner, S. B. ( 1991; ). Molecular biology of prion diseases. Science 252, 1515–1522.[CrossRef]
    [Google Scholar]
  37. Race, R. & Chesebro, B. ( 1998; ). Scrapie infectivity found in resistant species. Nature 392, 770.[CrossRef]
    [Google Scholar]
  38. Race, R., Jenny, A. & Sutton, D. ( 1998; ). Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: implications for transmission and antemortem diagnosis. J Infect Dis 178, 949–953.[CrossRef]
    [Google Scholar]
  39. Race, R., Raines, A., Raymond, G. J., Caughey, B. & Chesebro, B. ( 2001; ). Long-term subclinical carrier state precedes scrapie replication and adaptation in a resistant species: analogies to bovine spongiform encephalopathy and variant Creutzfeldt–Jakob disease in humans. J Virol 75, 10106–10112.[CrossRef]
    [Google Scholar]
  40. 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.[CrossRef]
    [Google Scholar]
  41. Schreuder, B. E., van Keulen, L. J., Vromans, M. E., Langeveld, J. P. & Smits, M. A. ( 1996; ). Preclinical test for prion diseases. Nature 381, 563.[CrossRef]
    [Google Scholar]
  42. van Keulen, L. J., Schreudrer, B. E., Meloen, R. H., Poelen-van den Berg, M., Moou-Harkes, G., Vromans, M. E. & Langeveld, J. P. ( 1995; ). Immunohistochemical detection and localization of prion protein in brain tissue of sheep with natural scrapie. Vet Pathol 32, 299–308.[CrossRef]
    [Google Scholar]
  43. van Keulen, L. J., Schreuder, B. E., Meloen, R. H., Mooij-Harkes, G., Vromans, M. E. & Langeveld, J. P. ( 1996; ). Immunohistochemical detection of prion in lymphoid tissues of sheep with natural scrapie. J Clin Microbiol 34, 1228–1231.
    [Google Scholar]
  44. van Keulen, L. J., Schreuder, B. E., Vromans, M. E., Langeveld, J. P. & Smits, M. A. ( 2000; ). Pathogenesis of natural scrapie in sheep. Arch Virol Suppl. 16, 57–71.
    [Google Scholar]
  45. Vilotte, J. L., Soulier, S., Essalmani, R. & 14 other authors ( 2001; ). Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine PrP. J Virol 75, 5977–5984.[CrossRef]
    [Google Scholar]
  46. Westaway, D., Zuliani, V., Cooper, C. M., Da Costa, M., Neuman, S., Jenny, A. L., Detwiler, L. & Prusiner, S. B. ( 1994; ). Homozygosity for prion protein alleles encoding glutamine-171 renders sheep susceptible to natural scrapie. Genes Dev 8, 959–969.[CrossRef]
    [Google Scholar]
  47. Wood, J. L. N., McGill, I. S., Done, S. H. & Bradley, R. ( 1997; ). Neuropathology of scrapie: a study of the distribution patterns of brain lesions in 222 cases of natural scrapie in sheep, 1982–1991. Vet Rec 140, 167–174.[CrossRef]
    [Google Scholar]
  48. Zlotnik, I. ( 1958; ). The histopathology of the brain stem of sheep affected with natural scrapie. J Comp Pathol 68, 148–165.[CrossRef]
    [Google Scholar]
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