1887

Abstract

In view of the established link between bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob disease and of the susceptibility of sheep to experimental BSE, the detection of potential cases of naturally occurring BSE in sheep has become of great importance. In this study, the immunohistochemical (IHC) phenotype of disease-associated prion protein (PrP) accumulation has been determined in the brain of 64 sheep, of various breeds and PrP genotypes, that had developed neurological disease after experimental BSE challenge with different inocula by a range of routes. Sheep BSE was characterized by neuron-associated intra- and extracellular PrP aggregates and by conspicuous and consistent deposits in the cytoplasm of microglia-like cells. The stellate PrP type was also prominent in most brain areas and marked linear deposits in the striatum and midbrain were distinctive. Sheep of the ARR/ARR and ARQ/AHQ genotypes displayed lower levels of PrP than other sheep, and intracerebral BSE challenge resulted in higher levels of PrP accumulating in the brain compared with other routes. The PrP genotype and the route of challenge also appeared to affect the incubation period of the disease, giving rise to complex combinations of magnitude of PrP accumulation and incubation period. Despite these differences, the phenotype of PrP accumulation was found to be very consistent across the different factors tested (notably after subpassage of BSE in sheep), thus highlighting the importance of detailed IHC examination of the brain of clinically affected sheep for the identification of potential naturally occurring ovine BSE.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.80299-0
2005-03-01
2020-10-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/86/3/vir860827.html?itemId=/content/journal/jgv/10.1099/vir.0.80299-0&mimeType=html&fmt=ahah

References

  1. 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]
  2. Benestad S. L., Sarradin P., Thu B., Schönheit J., Tranulis M. A., 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]
  3. Bossers A., Belt P. B. G. M., Raymond G. J., Caughey B., de Vries R., Smits M. A. 1997; Scrapie susceptibility-linked polymorphisms modulate the in vitro conversion of sheep prion protein to protease-resistant forms. Proc Natl Acad Sci U S A 94:4931–4936 [CrossRef]
    [Google Scholar]
  4. Bossers A., de Vries R., Smits M. A. 2000; Susceptibility of sheep for scrapie as assessed by in vitro conversion of nine naturally occurring variants of PrP. J Virol 74:1407–1414 [CrossRef]
    [Google Scholar]
  5. Brown D. A., Bruce M. E., Fraser J. R. 2003; Comparison of the neuropathological characteristics of bovine spongiform encephalopathy (BSE) and variant Creutzfeldt–Jakob disease (vCJD) in mice. Neuropathol Appl Neurobiol 29:262–272 [CrossRef]
    [Google Scholar]
  6. Bruce M., 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 B Biol Sci 343:405–411 [CrossRef]
    [Google Scholar]
  7. Bruce M. E., Will R. G., Ironside J. W. 10 other authors 1997; Transmission to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature 389:498–501 [CrossRef]
    [Google Scholar]
  8. 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]
  9. DeArmond S. J., Ironside J. W. 1999; Neuropathology of prion diseases. In Prion Biology and Diseases pp  585–652 Edited by Prusiner S. B. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory;
    [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 [CrossRef]
    [Google Scholar]
  11. Foster J. D., Bruce M., McConnell I., Chree A., Fraser H. 1996; Detection of BSE infectivity in brain and spleen of experimentally infected sheep. Vet Rec 138:546–548 [CrossRef]
    [Google Scholar]
  12. Foster J. D., Parnham D. W., Hunter N., Bruce M. 2001; Distribution of the prion protein in sheep terminally affected with BSE following experimental oral transmission. J Gen Virol 82:2319–2326
    [Google Scholar]
  13. 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 [CrossRef]
    [Google Scholar]
  14. Fraser H., Bruce M. E., Chree A., McConnell I., Wells G. A. H. 1992; Transmission of bovine spongiform encephalopathy and scrapie to mice. J Gen Virol 73:1891–1897 [CrossRef]
    [Google Scholar]
  15. 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]
  16. González L., Martin S., Hunter N., Houston F., Simmons M. M., Bellworthy S. J., Ryder S. J., Jeffrey M. 2003a; Distinct profiles of disease-specific PrP accumulation are present in the brains of sheep affected with BSE and different scrapie sources. In Recent Progress in Transmissible Spongiform Encephalopathies Edited by Fraser J. R. Neuropathol Appl Neurobiol 29, 207–208 (available at) http://www.blackwellpublishing.com/products/journals/suppmat/nan/nan477/NAN477sm.pdf [CrossRef]
    [Google Scholar]
  17. González L., Martin S., Jeffrey M. 2003b; 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]
  18. Hadlow W. J., Race R. E., Kennedy R. C. 1987; Experimental infection of sheep and goats with transmissible mink encephalopathy virus. Can J Vet Res 51:135–144
    [Google Scholar]
  19. Hill A. F., Desbruslais M., Joiner S., Sidle K. C. L., Gowland I., Collinge J., Doey L. J., Lantos P. 1997; The same prion strain causes vCJD and BSE. Nature 389:448–450 [CrossRef]
    [Google Scholar]
  20. Hope J., Wood S. C. E. R., Birkett C. R., Chong A., Bruce M. E., Cairns D., Goldmann W., Hunter N., Bostock C. J. 1999; Molecular analysis of ovine prion protein identifies similarities between BSE and an experimental isolate of natural scrapie, CH1641. J Gen Virol 80:1–4
    [Google Scholar]
  21. Houston F., Foster J. D., Chong A., Hunter N., Bostock C. J. 2000; Transmission of BSE by blood transfusion in sheep. Lancet 356:999–1000 [CrossRef]
    [Google Scholar]
  22. 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]
  23. 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]
  24. Jeffrey M., Wells G. A. H. 1988; Spongiform encephalopathy in a nyala ( Tragelaphus angasi . Vet Pathol 25:398–399 [CrossRef]
    [Google Scholar]
  25. 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 [CrossRef]
    [Google Scholar]
  26. 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 [CrossRef]
    [Google Scholar]
  27. 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]
  28. Jeffrey M., Ryder S., Martin S., Hawkins S. A. C., Terry L., Berthelin-Baker C., Bellworthy S. J. 2001b; 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]
  29. 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]
  30. Lasmézas C. I., Deslys J.-P., Demaimay R., Adjou K. T., Lamoury F., Dormont D., Robain O., Ironside J., Hauw J.-J. 1996; BSE transmission to macaques. Nature 381:743–744 [CrossRef]
    [Google Scholar]
  31. 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]
  32. Martin S., González L., Chong A., Houston F. E., Hunter N., Jeffrey M. 2005; Immunohistochemical characteristics of disease-associated PrP are not altered by host genotype or route of inoculation following infection of sheep with bovine spongiform encephalopathy. J Gen Virol 86:839–848 [CrossRef]
    [Google Scholar]
  33. Ryder S. J., Hawkins S. A. C., Dawson M., Wells G. A. H. 2000; The neuropathology of experimental bovine spongiform encephalopathy in the pig. J Comp Pathol 122:131–143 [CrossRef]
    [Google Scholar]
  34. Schreuder B. E. C., Somerville R. A. 2003; Bovine spongiform encephalopathy in sheep?. Rev Sci Tech 22:103–120
    [Google Scholar]
  35. Scott M. R., Will R., Ironside J., Nguyen H.-O. B., Tremblay P., DeArmond S. J., Prusiner S. B. 1999; Compelling transgenetic evidence for transmission of bovine spongiform encephalopathy prions to humans. Proc Natl Acad Sci U S A 96:15137–15142 [CrossRef]
    [Google Scholar]
  36. Somerville R. A. 1999; Host and transmissible spongiform encephalopathy agent strain control glycosylation of PrP. J Gen Virol 80:1865–1872
    [Google Scholar]
  37. 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]
  38. 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]
  39. Wells G. A. H., McGill I. S. 1992; Recently described scrapie-like encephalopathies of animals: case definitions. Res Vet Sci 53:1–10 [CrossRef]
    [Google Scholar]
  40. Wells G. A. H., Wilesmith J. W. 1995; The neuropathology and epidemiology of bovine spongiform encephalopathy. Brain Pathol 5:91–103 [CrossRef]
    [Google Scholar]
  41. Wyatt J. M., Pearson G. R., Smerdon T. N., Gruffydd-Jones T. J., Wells G. A. H., Wilesmith J. W. 1991; Naturally occurring scrapie-like spongiform encephalopathy in five domestic cats. Vet Rec 129:233–236 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.80299-0
Loading
/content/journal/jgv/10.1099/vir.0.80299-0
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

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