1887

Journal of General Virology header logo

Volume 92, Issue 6

Emergence of multiple prion strains from single isolates of ovine scrapie Free

Abstract

The infectious agent associated with prion diseases such as ovine scrapie shows strain diversity. Ovine prion strains have typically been identified by their transmission properties in wild-type mice. However, strain typing of ovine scrapie isolates in wild-type mice may not reveal properties of the infectious prion agent as they exist in the original host. This could be circumvented if ovine scrapie isolates are passaged in ovine prion protein (PrP)-transgenic mice. This study used incubation time, lesion profile, immunohistochemistry of the disease-associated PrP (PrP) and molecular profile to compare the range of ovine prion strains that emerged from sheep scrapie isolates following serial passage in wild-type and ovine PrP transgenic mice. It was found that a diverse range of ovine prion strains emerged from homozygous ARQ and VRQ scrapie isolates passaged in wild-type and ovine PrP transgenic mice. However, strain-specific PrP deposition and PrP27–30 molecular profile patterns were identified in ovine PrP transgenic mice that were not detected in wild-type mice. Significantly, it was established that the individual mouse brain selected for transmission during prion strain typing had a significant influence on strain definition. Serial passage of short- and long-incubation-time animals from the same group of scrapie-inoculated mice revealed different prion strain phenotypes. These observations are consistent with the possibility that some scrapie isolates contain more than one prion strain.

  • Received:
  • Accepted:
  • Published Online:
© 2011 Crown copyright
Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.028886-0
2011-06-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/92/6/1482.html?itemId=/content/journal/jgv/10.1099/vir.0.028886-0&mimeType=html&fmt=ahah

References

  1. Aguzzi A., Polymenidou M. 2004; Mammalian prion biology: one century of evolving concepts. Cell 116:313–327 [View Article][PubMed]
     [Google Scholar]
  2. Alper T., Haig D. A., Clarke M. C. 1966; The exceptionally small size of the scrapie agent. Biochem Biophys Res Commun 22:278–284 [View Article][PubMed]
     [Google Scholar]
  3. Alper T., Cramp W. A., Haig D. A., Clarke M. C. 1967; Does the agent of scrapie replicate without nucleic acid?. Nature 214:764–766 [View Article][PubMed]
     [Google Scholar]
  4. Bartz J. C., Bessen R. A., McKenzie D., Marsh R. F., Aiken J. M. 2000; Adaptation and selection of prion protein strain conformations following interspecies transmission of transmissible mink encephalopathy. J Virol 74:5542–5547 [View Article][PubMed]
     [Google Scholar]
  5. Beck K. E., Chaplin M., Stack M., Sallis R. E., Simonini S., Lockey R., Spiropoulos J. 2010a). Lesion profiling at primary isolation in RIII mice is insufficient in distinguishing BSE from classical scrapie. Brain Pathol 20:313–322 [View Article][PubMed]
     [Google Scholar]
  6. Beck K. E., Sallis R. E., Lockey R., Simmons M. M., Spiropoulos J. 2010b). Ovine PrP genotype is linked with lesion profile and immunohistochemistry patterns after primary transmission of classical scrapie to wild-type mice. J Neuropathol Exp Neurol 69:483–497 [View Article][PubMed]
     [Google Scholar]
  7. Bessen R. A., Marsh R. F. 1992; Biochemical and physical properties of the prion protein from two strains of the transmissible mink encephalopathy agent. J Virol 66:2096–2101[PubMed]
     [Google Scholar]
  8. Bruce M. E. 1993; Scrapie strain variation and mutation. Br Med Bull 49:822–838[PubMed]
     [Google Scholar]
  9. Bruce M. E. 2003; TSE strain variation. Br Med Bull 66:99–108 [View Article][PubMed]
     [Google Scholar]
  10. Bruce M. E., Dickinson A. G. 1987; Biological evidence that scrapie agent has an independent genome. J Gen Virol 68:79–89 [View Article][PubMed]
     [Google Scholar]
  11. Bruce M. E., Boyle A., Cousens S., McConnell I., Foster J., Goldmann W., Fraser H. 2002; Strain characterization of natural sheep scrapie and comparison with BSE. J Gen Virol 83:695–704[PubMed]
     [Google Scholar]
  12. Castilla J., Saá P., Hetz C., Soto C. 2005; In vitro generation of infectious scrapie prions. Cell 121:195–206 [View Article][PubMed]
     [Google Scholar]
  13. Chesebro B. 1998; BSE and prions: uncertainties about the agent. Science 279:42–43 [View Article][PubMed]
     [Google Scholar]
  14. Colby D. W., Giles K., Legname G., Wille H., Baskakov I. V., DeArmond S. J., Prusiner S. B. 2009; Design and construction of diverse mammalian prion strains. Proc Natl Acad Sci U S A 106:20417–20422 [View Article][PubMed]
     [Google Scholar]
  15. Colby D. W., Wain R., Baskakov I. V., Legname G., Palmer C. G., Nguyen H. O., Lemus A., Cohen F. E., DeArmond S. J., Prusiner S. B. 2010; Protease-sensitive synthetic prions. PLoS Pathog 6:e1000736 [View Article][PubMed]
     [Google Scholar]
  16. Collinge J. 2001; Prion diseases of humans and animals: their causes and molecular basis. Annu Rev Neurosci 24:519–550 [View Article][PubMed]
     [Google Scholar]
  17. Collinge J., Clarke A. R. 2007; A general model of prion strains and their pathogenicity. Science 318:930–936 [View Article][PubMed]
     [Google Scholar]
  18. Cordier C., Bencsik A., Philippe S., Bétemps D., Ronzon F., Calavas D., Crozet C., Baron T. 2006; Transmission and characterization of bovine spongiform encephalopathy sources in two ovine transgenic mouse lines (TgOvPrP4 and TgOvPrP59). J Gen Virol 87:3763–3771 [View Article][PubMed]
     [Google Scholar]
  19. Deleault N. R., Harris B. T., Rees J. R., Supattapone S. 2007; Formation of native prions from minimal components in vitro . Proc Natl Acad Sci U S A 104:9741–9746 [View Article][PubMed]
     [Google Scholar]
  20. Dickinson A. G. 1976; Scrapie in sheep and goats. In Slow Virus Diseases of Animals and Man Amsterdam: North-Holland;
     [Google Scholar]
  21. Eloit M., Adjou K., Coulpier M., Fontaine J. J., Hamel R., Lilin T., Messiaen S., Andreoletti O., Baron T. et al. 2005; BSE agent signatures in a goat. Vet Rec 156:523–524[PubMed] [CrossRef]
     [Google Scholar]
  22. Farquhar C. F., Somerville R. A., Bruce M. E. 1998; Straining the prion hypothesis. Nature 391:345–346 [View Article][PubMed]
     [Google Scholar]
  23. Féraudet C., Morel N., Simon S., Volland H., Frobert Y., Créminon C., Vilette D., Lehmann S., Grassi J. 2005; Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells. J Biol Chem 280:11247–11258 [View Article][PubMed]
     [Google Scholar]
  24. Fraser H., Dickinson A. G. 1968; The sequential development of the brain lesion of scrapie in three strains of mice. J Comp Pathol 78:301–311 [View Article][PubMed]
     [Google Scholar]
  25. 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 [View Article][PubMed]
     [Google Scholar]
  26. Gambetti P., Kong Q., Zou W., Parchi P., Chen S. G. 2003; Sporadic and familial CJD: classification and characterisation. Br Med Bull 66:213–239 [View Article][PubMed]
     [Google Scholar]
  27. Hill A. F., Joiner S., Wadsworth J. D., Sidle K. C., Bell J. E., Budka H., Ironside J. W., Collinge J. 2003; Molecular classification of sporadic Creutzfeldt–Jakob disease. Brain 126:1333–1346 [View Article][PubMed]
     [Google Scholar]
  28. 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 [View Article][PubMed]
     [Google Scholar]
  29. Legname G., Nguyen H. O., Baskakov I. V., Cohen F. E., Dearmond S. J., Prusiner S. B. 2005; Strain-specified characteristics of mouse synthetic prions. Proc Natl Acad Sci U S A 102:2168–2173 [View Article][PubMed]
     [Google Scholar]
  30. Li J., Browning S., Mahal S. P., Oelschlegel A. M., Weissmann C. 2010; Darwinian evolution of prions in cell culture. Science 327:869–872 [View Article][PubMed]
     [Google Scholar]
  31. Makarava N., Baskakov I. V. 2008; The same primary structure of the prion protein yields two distinct self-propagating states. J Biol Chem 283:15988–15996 [View Article][PubMed]
     [Google Scholar]
  32. Makarava N., Ostapchenko V. G., Savtchenko R., Baskakov I. V. 2009; Conformational switching within individual amyloid fibrils. J Biol Chem 284:14386–14395 [View Article][PubMed]
     [Google Scholar]
  33. Makarava N., Kovacs G. G., Bocharova O., Savtchenko R., Alexeeva I., Budka H., Rohwer R. G., Baskakov I. V. 2010; Recombinant prion protein induces a new transmissible prion disease in wild-type animals. Acta Neuropathol 119:177–187 [View Article][PubMed]
     [Google Scholar]
  34. Mazza M., Iulini B., Vaccari G., Acutis P. L., Martucci F., Esposito E., Peletto S., Barocci S., Chiappini B., Corona C. 2010; Co-existence of classical scrapie and Nor98 in a sheep from an Italian outbreak. Res Vet Sci 88:478–485 [View Article][PubMed]
     [Google Scholar]
  35. Polymenidou M., Stoeck K., Glatzel M., Vey M., Bellon A., Aguzzi A. 2005; Coexistence of multiple PrPSc types in individuals with Creutzfeldt–Jakob disease. Lancet Neurol 4:805–814 [View Article][PubMed]
     [Google Scholar]
  36. Prusiner S. B. 1982; Novel proteinaceous infectious particles cause scrapie. Science 216:136–144 [View Article][PubMed]
     [Google Scholar]
  37. Prusiner S. B. 2004 Prion Biology and Diseases, 2nd edn. Cold Spring Harbour, NY: Cold Spring Harbor Laboratory;
     [Google Scholar]
  38. Saá P., Castilla J., Soto C. 2006; Ultra-efficient replication of infectious prions by automated protein misfolding cyclic amplification. J Biol Chem 281:35245–35252 [View Article][PubMed]
     [Google Scholar]
  39. Safar J. G., Kellings K., Serban A., Groth D., Cleaver J. E., Prusiner S. B., Riesner D. 2005; Search for a prion-specific nucleic acid. J Virol 79:10796–10806 [View Article][PubMed]
     [Google Scholar]
  40. Thackray A. M., Hopkins L., Bujdoso R. 2007; Proteinase K-sensitive disease-associated ovine prion protein revealed by conformation-dependent immunoassay. Biochem J 401:475–483 [View Article][PubMed]
     [Google Scholar]
  41. Thackray A. M., Hopkins L., Spiropoulos J., Bujdoso R. 2008; Molecular and transmission characteristics of primary-passaged ovine scrapie isolates in conventional and ovine PrP transgenic mice. J Virol 82:11197–11207 [View Article][PubMed]
     [Google Scholar]
  42. Vilotte J. L., Soulier S., Essalmani R., Stinnakre M. G., Vaiman D., Lepourry L., Da Silva J. C., Besnard N., Dawson M. et al. 2001; Markedly increased susceptibility to natural sheep scrapie of transgenic mice expressing ovine PrP. J Virol 75:5977–5984 [View Article][PubMed]
     [Google Scholar]
  43. Wang F., Wang X., Yuan C.-G., Ma J. 2010; Generating a prion with bacterially expressed recombinant prion protein. Science 327:1132–1135 [View Article][PubMed]
     [Google Scholar]
  44. Weber P., Giese A., Piening N., Mitteregger G., Thomzig A., Beekes M., Kretzschmar H. A. 2007; Generation of genuine prion infectivity by serial PMCA. Vet Microbiol 123:346–357 [View Article][PubMed]
     [Google Scholar]
  45. Yokoyama T., Masujin K., Schmerr M. J., Shu Y., Okada H., Iwamaru Y., Imamura M., Matsuura Y., Murayama Y., Mohri S. 2010; Intraspecies prion transmission results in selection of sheep scrapie strains. PLoS ONE 5:e15450 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.028886-0
Loading
Emergence of multiple prion strains from single isolates of ovine scrapie
J. Gen. Virol. 92, 1482 (2011); https://doi.org/10.1099/vir.0.028886-0
/content/journal/jgv/10.1099/vir.0.028886-0
/content/journal/jgv/10.1099/vir.0.028886-0
Loading

Data & Media loading...

Most cited 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