Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 19, Number 11—November 2013
Research

Atypical Scrapie Prions from Sheep and Lack of Disease in Transgenic Mice Overexpressing Human Prion Protein

Jonathan D.F. WadsworthComments to Author , Susan Joiner, Jacqueline M. Linehan, Anne Balkema-Buschmann, John Spiropoulos, Marion M. Simmons, Peter C. Griffiths, Martin H. Groschup, James Hope, Sebastian Brandner, Emmanuel A. Asante, and John Collinge
Author affiliations: University College London, London, UK (J.D.F Wadsworth, S. Joiner, J.M. Linehan, S. Brandner, E.A. Asante, J. Collinge); Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany (A. Anne Balkema-Buschmann, M.H. Groschup); Animal Health and Veterinary Laboratories Agency, Addlestone, UK (J. Spiropoulos, M.M. Simmons, P.C. Griffiths, J. Hope)

Main Article

Table 1

Details of prion sources for ovine inocula*

Source code Brain region Prion agent Ovine PrP genotype‡
Transmission data†
Attack rate (incubation period) Reference
AHVLA/SE 1919/0077 Cerebral cortex Classical scrapie VRQ/VRQ tg338 mice§; 16/16 (64 ± 2 d) (21); code SE 1848/0005
AHVLA/SE 1919/0080 Cerebral cortex Classical scrapie ARQ/ARQ tg338 mice§ 12/13 (155 ± 4 d) (21); code SE 1848/0008
FLI 1/06 Caudal medulla Classical scrapie ARQ/ARQ ND NA
FLI 83/04 Caudal medulla Classical scrapie ARQ/ARQ ND NA
FLI 107/04 Caudal medulla Classical scrapie ARQ/ARQ ND NA
AHVLA/SE 1850/0001 Caudal medulla Atypical scrapie AHQ/AHQ tg338 mice§; 19/20 (210 ± 3 d) (22); code 1
AHVLA/SE 1850/0009 Caudal medulla Aypical scrapie ARR/ARR tg338 mice§; 19/19 (231 ± 6 d) (22); code 9
FLI S7/06 Caudal medulla Atypical scrapie AHQ/ARQ ND NA
FLI 14/06 Caudal medulla Atypical scrapie ARR/ARR ND NA
FLI 26/06 Caudal medulla Atypical scrapie AHQ/ARQ ND NA
AHVLA/SE 1929/0877 Caudal medulla Ovine BSE ARQ/ARQ RIII mice; 16/19 (422 ± 19 d)¶ Unpub.
AHVLA/SE1945/0032 Rostral medulla 2nd Passage ovine BSE ARQ/ARQ RIII mice; 18/20 (356 ± 9 d)¶ Unpub.

*PrP, prion protein; AHVLA, Animal Health and Veterinary Laboratories Agency; ND, not done; NA, not applicable; FLI, Friedrich-Loeffler-Institut; BSE, bovine spongiform encephalopathy; Unpub., unpublished.
†Reports attack rate (the no. of infected mice as a proportion of the no. of inoculated mice) and mean incubation period in days ± SEM or SD and the reference in which the data were first published with original inocula code.
‡Ovine PrP codon 136,154,171 genotype.
§Transgenic for the ovine Prnp VRQ allele on a mouse Prnp0/0 background. Overexpression 8- to 10-fold of normal ovine brain.
¶Mean incubation period in days ± SEM.

Main Article

References
  1. Collinge  J, Sidle  KC, Meads  J, Ironside  J, Hill  AF. Molecular analysis of prion strain variation and the aetiology of ‘new variant’ CJD. Nature. 1996;383:68590. DOIPubMedGoogle Scholar
  2. Hill  AF, Desbruslais  M, Joiner  S, Sidle  KCL, Gowland  I, Collinge  J. The same prion strain causes vCJD and BSE. Nature. 1997;389:44850. DOIPubMedGoogle Scholar
  3. Bruce  ME, Will  RG, Ironside  JW, McConnell  I, Drummond  D, Suttie  A, Transmissions to mice indicate that ‘new variant’ CJD is caused by the BSE agent. Nature. 1997;389:498501. DOIPubMedGoogle Scholar
  4. Asante  EA, Linehan  J, Desbruslais  M, Joiner  S, Gowland  I, Wood  A, BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J. 2002;21:635866. DOIPubMedGoogle Scholar
  5. Collinge  J, Whitfield  J, McKintosh  E, Beck  J, Mead  S, Thomas  DJ, Kuru in the 21st century—an acquired human prion disease with very long incubation periods. Lancet. 2006;367:206874. DOIPubMedGoogle Scholar
  6. Hilton  DA, Ghani  AC, Conyers  L, Edwards  P, McCardle  L, Ritchie  D, Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol. 2004;203:7339. DOIPubMedGoogle Scholar
  7. Clewley  JP, Kelly  CM, Andrews  N, Vogliqi  K, Mallinson  G, Kaisar  M, Prevalence of disease related prion protein in anonymous tonsil specimens in Britain: cross sectional opportunistic survey. BMJ. 2009;338:b1442. DOIPubMedGoogle Scholar
  8. UK Health Protection Agency. Summary results of the second national survey of abnormal prion prevalence in archived appendix specimens. Heath Protection Agency Report. News Archives. 2012;6:32 [cited 2012 Aug 10]. http://www.hpa.org.uk/hpr/archives/2012/news3212.htm#bnrmlp
  9. Eloit  M, Adjou  K, Coulpier  M, Fontaine  JJ, Hamel  R, Lilin  T, BSE agent signatures in a goat. Vet Rec. 2005;156:5234 .PubMedGoogle Scholar
  10. Spiropoulos  J, Lockey  R, Sallis  RE, Terry  LA, Thorne  L, Holder  TM, Isolation of prion with BSE properties from farmed goat. Emerg Infect Dis. 2011;17:225361. DOIPubMedGoogle Scholar
  11. European Food Safety AuthorityPanel on Biological Hazards (BIOHAZ). Joint scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans. EFSA Journal. 2011;9:1945–2056 [cited 11 Sep 2013]. http://www.efsa.europa.eu/en/publications/efsajournal.htm
  12. Benestad  SL, Sarradin  P, Thu  B, Schonheit  J, Tranulis  MA, Bratberg  B. Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec. 2003;153:2028. DOIPubMedGoogle Scholar
  13. Benestad  SL, Arsac  JN, Goldmann  W, Noremark  M. Atypical/Nor98 scrapie: properties of the agent, genetics, and epidemiology. Vet Res. 2008;39:19. DOIPubMedGoogle Scholar
  14. Webb  PR, Powell  L, Denyer  M, Marsh  S, Weaver  C, Simmons  MM, A retrospective immunohistochemical study reveals atypical scrapie has existed in the United Kingdom since at least 1987. J Vet Diagn Invest. 2009;21:8269. DOIPubMedGoogle Scholar
  15. Bruce  ME, Nonno  R, Foster  J, Goldmann  W, Di Bari  M, Esposito  E, Nor98-like sheep scrapie in the United Kingdom in 1989. Vet Rec. 2007;160:6656. DOIPubMedGoogle Scholar
  16. Wadsworth  JD, Asante  EA, Collinge  J. Contribution of transgenic models to understanding human prion disease. Neuropathol Appl Neurobiol. 2010;36:57697. DOIPubMedGoogle Scholar
  17. Padilla  D, Beringue  V, Espinosa  JC, Andreoletti  O, Jaumain  E, Reine  F, Sheep and goat BSE propagate more efficiently than cattle BSE in human PrP transgenic mice. PLoS Pathog. 2011;7:e1001319. DOIPubMedGoogle Scholar
  18. Kong  Q, Huang  S, Zou  W, Vanegas  D, Wang  M, Wu  D, Chronic wasting disease of elk: transmissibility to humans examined by transgenic mouse models. J Neurosci. 2005;25:79449. DOIPubMedGoogle Scholar
  19. Tamgüney  G, Giles  K, Bouzamondo-Bernstein  E, Bosque  PJ, Miller  MW, Safar  J, Transmission of elk and deer prions to transgenic mice. J Virol. 2006;80:910414. DOIPubMedGoogle Scholar
  20. Sandberg  MK, Al Doujaily  H, Sigurdson  CJ, Glatzel  M, O’Malley  C, Powell  C, Chronic wasting disease prions are not transmissible to transgenic mice overexpressing human prion protein. J Gen Virol. 2010;91:26517. DOIPubMedGoogle Scholar
  21. Thackray  AM, Hopkins  L, Spiropoulos  J, Bujdoso  R. Molecular and transmission characteristics of primary passaged ovine scrapie isolates in conventional and ovine PrP transgenic mice. J Virol. 2008;82:11197207. DOIPubMedGoogle Scholar
  22. Griffiths  PC, Spiropoulos  J, Lockey  R, Tout  AC, Jayasena  D, Plater  JM, Characterisation of atypical scrapie cases from Great Britain in transgenic ovine PrP mice. J Gen Virol. 2010;91:21328. DOIPubMedGoogle Scholar
  23. Lloyd  SE, Linehan  J, Desbruslais  M, Joiner  S, Buckell  J, Brandner  S, Characterization of two distinct prion strains derived from bovine spongiform encephalopathy transmissions to inbred mice. J Gen Virol. 2004;85:24718. DOIPubMedGoogle Scholar
  24. Wadsworth  JD, Asante  EA, Desbruslais  M, Linehan  J, Joiner  S, Gowland  I, Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science. 2004;306:17936. DOIPubMedGoogle Scholar
  25. Asante  EA, Linehan  J, Gowland  I, Joiner  S, Fox  K, Cooper  S, Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc Natl Acad Sci U S A. 2006;103:1075964. DOIPubMedGoogle Scholar
  26. Wadsworth  JD, Joiner  S, Linehan  JM, Desbruslais  M, Fox  K, Cooper  S, Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice. Proc Natl Acad Sci U S A. 2008;105:388590. DOIPubMedGoogle Scholar
  27. Wadsworth  JD, Powell  C, Beck  JA, Joiner  S, Linehan  JM, Brandner  S, Molecular diagnosis of human prion disease. Methods Mol Biol. 2008;459:197227. DOIPubMedGoogle Scholar
  28. Wadsworth  JD, Joiner  S, Hill  AF, Campbell  TA, Desbruslais  M, Luthert  PJ, Tissue distribution of protease resistant prion protein in variant CJD using a highly sensitive immuno-blotting assay. Lancet. 2001;358:17180. DOIPubMedGoogle Scholar
  29. Kascsak  RJ, Rubenstein  R, Merz  PA, Tonna DeMasi  M, Fersko  R, Carp  RI, Mouse polyclonal and monoclonal antibody to scrapie-associated fibril proteins. J Virol. 1987;61:368893 .PubMedGoogle Scholar
  30. Safar  J, Wille  H, Itri  V, Groth  D, Serban  H, Torchia  M, Eight prion strains have PrPSc molecules with different conformations. Nat Med. 1998;4:115765. DOIPubMedGoogle Scholar
  31. Gretzschel  A, Buschmann  A, Eiden  M, Ziegler  U, Luhken  G, Erhardt  G, Strain typing of German transmissible spongiform encephalopathies field cases in small ruminants by biochemical methods. J Vet Med B Infect Dis Vet Public Health. 2005;52:5563. DOIPubMedGoogle Scholar
  32. Gretzschel  A, Buschmann  A, Langeveld  J, Groschup  MH. Immunological characterization of abnormal prion protein from atypical scrapie cases in sheep using a panel of monoclonal antibodies. J Gen Virol. 2006;87:371522. DOIPubMedGoogle Scholar
  33. Hill  AF, Joiner  S, Wadsworth  JD, Sidle  KC, Bell  JE, Budka  H, Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain. 2003;126:133346. DOIPubMedGoogle Scholar
  34. Plinston  C, Hart  P, Chong  A, Hunter  N, Foster  J, Piccardo  P, Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy following passage in sheep. J Virol. 2011;85:117481 . DOIPubMedGoogle Scholar
  35. Wilson  R, Plinston  C, Hunter  N, Casalone  C, Corona  C, Tagliavini  F, Chronic wasting disease and atypical forms of BSE and scrapie are not transmissible to mice expressing wild-type levels of human PrP. J Gen Virol. 2012;93:16249 . DOIPubMedGoogle Scholar
  36. Bishop  MT, Hart  P, Aitchison  L, Baybutt  HN, Plinston  C, Thomson  V, Predicting susceptibility and incubation time of human-to-human transmission of vCJD. Lancet Neurol. 2006;5:3938 . DOIPubMedGoogle Scholar
  37. Götte  DR, Benestad  SL, Laude  H, Zurbriggen  A, Oevermann  A, Seuberlich  T. Atypical scrapie isolates involve a uniform prion species with a complex molecular signature. PLoS ONE. 2011;6:e27510 . DOIPubMedGoogle Scholar
  38. Béringue  V, Herzog  L, Jaumain  E, Reine  F, Sibille  P, Le Dur  A, Facilitated cross-species transmission of prions in extraneural tissue. Science. 2012;335:4725 . DOIPubMedGoogle Scholar

Main Article

Page created: October 31, 2013
Page updated: October 31, 2013
Page reviewed: October 31, 2013
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external