1887

Abstract

Scrapie of sheep and goats is the most common prion disease (or transmissible spongiform encephalopathy, TSE) of mammals and aggregates of abnormal, proteinase-resistant prion protein (PrP) are found in all naturally occurring prion diseases. During active surveillance of British sheep for TSEs, 29 201 sheep brain stem samples were collected from abattoirs and analysed for the presence of PrP. Of these samples, 54 were found to be positive by using an ELISA screening test, but 28 of these could not be confirmed initially by immunohistochemistry. These unconfirmed or atypical cases were generally found in PrP genotypes normally associated with relative resistance to clinical scrapie and further biochemical analysis revealed that they contained forms of PrP with a relatively protease-sensitive amyloid core, some resembling those of Nor98 scrapie. The presence of these atypical forms of protease-resistant PrP raises concerns that some TSE disorders of PrP metabolism previously may have escaped identification in the British sheep population.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.81539-0
2006-02-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/87/2/471.html?itemId=/content/journal/jgv/10.1099/vir.0.81539-0&mimeType=html&fmt=ahah

References

  1. Barron R. M., Thomson V., King D., Shaw J., Melton D. W., Manson J. C. 2003; Transmission of murine scrapie to P101L transgenic mice. J Gen Virol 84:3165–3172 [CrossRef]
    [Google Scholar]
  2. Baylis M., McIntyre K. M. 2004; Transmissible spongiform encephalopathies: scrapie control under new strain. Nature 432:810–811 [CrossRef]
    [Google Scholar]
  3. Benestad S. L., Sarradin P., Thu B., Schonheit 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]
  4. Bolton D. C., McKinley M. P., Prusiner S. B. 1982; Identification of a protein that co-purifies with the scrapie prion. Science 218:1309–1311 [CrossRef]
    [Google Scholar]
  5. Bolton D. C., Rudelli R. D., Currie J. R., Bendheim P. E. 1991; Copurification of Sp33-37 and scrapie agent from hamster brain prior to detectable histopathology and clinical disease. J Gen Virol 72:2905–2913 [CrossRef]
    [Google Scholar]
  6. Buschmann A., Biacabe A.-G., Ziegler U., Bencsik A., Madec J.-Y., Erhardt G., Lühken G., Baron T., Groschup M. H. 2004; Atypical scrapie cases in Germany and France are identified by discrepant reaction patterns in BSE rapid tests. J Virol Methods 117:27–36 [CrossRef]
    [Google Scholar]
  7. Castilla J., Saá P., Hetz C., Soto C. 2005; In vitro generation of infectious scrapie prions. Cell 121:195–206 [CrossRef]
    [Google Scholar]
  8. Czub M., Braig H. R., Diringer H. 1986; Pathogenesis of scrapie: study of the temporal development of clinical symptoms, of infectivity titres and scrapie-associated fibrils in brains of hamsters infected intraperitoneally. J Gen Virol 67:2005–2009 [CrossRef]
    [Google Scholar]
  9. Czub M., Braig H. R., Diringer H. 1988; Replication of the scrapie agent in hamsters infected intracerebrally confirms the pathogenesis of an amyloid-inducing virosis. J Gen Virol 69:1753–1756 [CrossRef]
    [Google Scholar]
  10. De Bosschere H., Roels S., Benestad S. L., Vanopdenbosch E. 2004; Scrapie case similar to Nor98 diagnosed in Belgium via active surveillance. Vet Rec 155:707–708 [CrossRef]
    [Google Scholar]
  11. Dobson C. M. 2005; Structural biology: prying into prions. Nature 435:747–749 [CrossRef]
    [Google Scholar]
  12. EFSA 2005; Scientific Report of the European Food Safety Authority on the evaluation of rapid post mortem TSE tests intended for small ruminants. EFSA J 31:1–17
    [Google Scholar]
  13. Elliott H., Gubbins S., Ryan J., Ryder S., Tongue S., Watkins G., Wilesmith J. W. 2005; Prevalence of scrapie in sheep in Great Britain estimated from abattoir surveys during 2002 and 2003. Vet Rec 157:418–419 [CrossRef]
    [Google Scholar]
  14. Fraser H. 1976; The pathology of natural and experimental scrapie. In Slow Virus Diseases of Animals and Man pp  267–305 Edited by Kimberlin R. H. Amsterdam: North-Holland Publishing Company;
    [Google Scholar]
  15. Gavier-Widen D., Noremark M., Benestad S., Simmons M., Renstrom L., Bratberg B., Elvander M., Segerstad C. H. 2004; Recognition of the Nor98 variant of scrapie in the Swedish sheep population. J Vet Diagn Invest 16:562–567 [CrossRef]
    [Google Scholar]
  16. Gilmour J. S., Bruce M. E., MacKellar A. 1986; Cerebrovascular amyloidosis in scrapie-affected sheep. Neuropathol Appl Neurobiol 12:173–183 [CrossRef]
    [Google Scholar]
  17. Goldmann W., Hunter N., Foster J. D., Salbaum J. M., Beyreuther K., Hope J. 1990; Two alleles of a neural protein gene linked to scrapie in sheep. Proc Natl Acad Sci U S A 87:2476–2480 [CrossRef]
    [Google Scholar]
  18. Goldmann W., Baylis M., Chihota C., Stevenson E., Hunter N. 2005; Frequencies of PrP gene haplotypes in British sheep flocks and the implications for breeding programmes. J Appl Microbiol 98:1294–1302 [CrossRef]
    [Google Scholar]
  19. Grassi J., Comoy E., Simon S. & 8 other authors 2001; Rapid test for the preclinical postmortem diagnosis of BSE in central nervous system tissue. Vet Rec 149:577–582 [CrossRef]
    [Google Scholar]
  20. 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]
  21. Harmeyer S., Pfaff E., Groschup M. H. 1998; Synthetic peptide vaccines yield monoclonal antibodies to cellular and pathological prion proteins of ruminants. J Gen Virol 79:937–945
    [Google Scholar]
  22. Hope J., Morton L. J. D., Farquhar C. F., Multhaup G., Beyreuther K., Kimberlin R. H. 1986; The major protein 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]
  23. 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]
  24. Houston F., Goldmann W., Chong A., Jeffrey M., González L., Foster J., Parnham D., Hunter N. 2003; Prion diseases: BSE in sheep bred for resistance to infection. Nature 423:498 [CrossRef]
    [Google Scholar]
  25. Hunter N. 1997; PrP genetics in sheep and the implications for scrapie and BSE. Trends Microbiol 5:331–334 [CrossRef]
    [Google Scholar]
  26. Jeffrey M., Goodsir C. M., Holliman A., Higgins R. J., Bruce M. E., McBride P. A., Fraser J. R. 1998; Determination of the frequency and distribution of vascular and parenchymal amyloid with polyclonal and N-terminal-specific PrP antibodies in scrapie-affected sheep and mice. Vet Rec 142:534–537 [CrossRef]
    [Google Scholar]
  27. Legname G., Baskakov I. V., Nguyen H.-O., Riesner D., Cohen F. E., DeArmond S. J., Prusiner S. B. 2004; Synthetic mammalian prions. Science 305:673–676 [CrossRef]
    [Google Scholar]
  28. Madec J.-Y., Simon S., Lezmi S., Bencsik A., Grassi J., Baron T. 2004; Abnormal prion protein in genetically resistant sheep from a scrapie-infected flock. J Gen Virol 85:3483–3486 [CrossRef]
    [Google Scholar]
  29. McKinley M. P., Bolton D. C., Prusiner S. B. 1983; A protease-resistant protein is a structural component of the scrapie prion. Cell 35:57–62 [CrossRef]
    [Google Scholar]
  30. Moum T., Olsaker I., Hopp P., Moldal T., Valheim M., Moum T., Benestad S. L. 2005; Polymorphisms at codons 141 and 154 in the ovine prion protein gene are associated with scrapie Nor98 cases. J Gen Virol 86:231–235 [CrossRef]
    [Google Scholar]
  31. Moynagh J., Schimmel H. 1999; Tests for BSE evaluated. Nature 400:105
    [Google Scholar]
  32. OIE Handbook 2004 Scrapie. In Manual of Standards for Diagnostic Tests and Vaccines Publ. Office International des Epizooties; Paris, France:
    [Google Scholar]
  33. Onnasch H., Gunn H. M., Bradshaw B. J., Benestad S. L., Bassett H. F. 2004; Two Irish cases of scrapie resembling Nor98. Vet Rec 155:636–637 [CrossRef]
    [Google Scholar]
  34. Orge L., Galo A., Machado C., Lima C., Ochoa C., Silva J., Ramos M., Simas J. P. 2004; Identification of putative atypical scrapie in sheep in Portugal. J Gen Virol 85:3487–3491 [CrossRef]
    [Google Scholar]
  35. Ottinger T., Simonsson M., Klingeborn M., Linne T. 2005; Western immunoblot mapping of a Swedish case of Nor 98 (abstract). In 2nd International Symposium on The New Prion Biology: basic science, diagnosis and therapy Istituo Veneto di Science, Lettere di Arte; Venice:
    [Google Scholar]
  36. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144 [CrossRef]
    [Google Scholar]
  37. 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 [CrossRef]
    [Google Scholar]
  38. Safar J. G., Geschwind M. D., Deering C. & 10 other authors 2005; Diagnosis of human prion disease. Proc Natl Acad Sci U S A 102:3501–3506 [CrossRef]
    [Google Scholar]
  39. Tagliavini F., Prelli F., Porro M. & 7 other authors 1994; Amyloid fibrils in Gerstmann–Sträussler–Scheinker disease (Indiana and Swedish kindreds) express only PrP peptides encoded by the mutant allele. Cell 79:695–703 [CrossRef]
    [Google Scholar]
  40. 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 [CrossRef]
    [Google Scholar]
  41. Wickner R. B. 1994; [URE3] as an altered URE2 protein: evidence for a prion analog in Saccharomyces cerevisiae . Science 264:566–569 [CrossRef]
    [Google Scholar]
  42. Wickner R. B., Edskes H. K., Roberts B. T., Baxa U., Pierce M. M., Ross E. D., Brachmann A. 2004; Prions: proteins as genes and infectious entities. Genes Dev 18:470–485 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.81539-0
Loading
/content/journal/jgv/10.1099/vir.0.81539-0
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF
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