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 26, Number 6—June 2020

Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice

Alba Marín-Moreno1, Alvina Huor1, Juan Carlos Espinosa, Jean Yves Douet, Patricia Aguilar-Calvo2, Naima Aron, Juan Píquer, Sévérine Lugan, Patricia Lorenzo, Cecile Tillier, Hervé Cassard, Olivier Andreoletti, and Juan María TorresComments to Author 
Author affiliations: Centro de Investigación en Sanidad Animal, Madrid, Spain (A. Marín-Moreno, J.C. Espinosa, P. Aguilar-Calvo, J. Píquer, P. Lorenzo, J.M. Torres); Interactions Hôte Agent Pathogène–École Nationale Vétérinaire de Toulouse, Toulouse, France (A. Huor, J.Y. Douet, N. Aron, S. Lugan, C. Tiller, H. Cassard, O. Andreoletti)

Main Article

Table 1

Transmission of H- and L-type BSE isolates to TgMet129, TgMet/Val129, and TgVal129 mice in a study of atypical BSE transmission using isolates from different countries in Europe and transgenic mouse models overexpressing human normal brain prion protein*

Isolate Mean survival period, dpi + SD (n/n0) (reference)†
P1 P2 P1 P2 P1 P2
C-BSE0 739 (1/6) (12,18) 633 + 32 (6/6) (18) >700 (0/6) (18) >700 (0/6) (18) >700 (0/6) (18) >700 (0/6) (18)
C-BSE2 491–707 (0/9) (12,18) 572 + 37 (3/4) (12,18) >700 (0/5) (18) ND >700 (0/6) (18) >700 (0/6) (18)
C-BSE3 758–801 (2/6) 615 + 95 (6/6) ND ND >700 (0/6) >700 (0/6)
BSE L1 607 + 13 (7/7) 487 + 116 (4/4) >700 (0/12) ND >700 (0/14) >700 (0/4)
BSE L1→TgMet129 487 + 116 (4/4) ND ND ND >700 (0/4) ND
BSE L2 629 + 35 (7/7) 508 + 97 (5/5) >700 (0/6) ND >700 (0/6) >700 (0/6)
BSE L2→TgMet129 508 + 97 (5/5) ND >700 (0/7) ND >700 (0/6) >700 (0/6)
BSE L3 541 + 70 (7/7) ND >700 (0/11) ND >700 (0/11) ND
BSE H1 >700 (0/19) >700 (0/6) >700 (0/14) ND >700 (0/13) >700 (0/6)
BSE H2 >700 (0/12) >700 (0/6) >700 (0/12) ND >700 (0/12) ND
BSE H3 >700 (0/14) >700 (0/12) >700 (0/12) ND >700 (0/12) ND

*BSE, bovine spongiform encephalopathy; C-BSE, classical bovine spongiform encephalopathy; dpi, days postinoculation; ND, not detected; n/n0, diseased proteinase K–resistant prion protein–positive/inoculated animals; P1, first passage; P2, second passage.
†Survival time is indicated as mean dpi + SD for all mice that scored positive for proteinase K–resistant prion protein.

Main Article

  1. Prusiner  SB. Prions. Proc Natl Acad Sci U S A. 1998;95:1336383. DOIPubMedGoogle Scholar
  2. Vázquez-Fernández  E, Vos  MR, Afanasyev  P, Cebey  L, Sevillano  AM, Vidal  E, et al. The structural architecture of an infectious mammalian prion using electron cryomicroscopy. PLoS Pathog. 2016;12:e1005835. DOIPubMedGoogle Scholar
  3. Gielbert  A, Davis  LA, Sayers  AR, Hope  J, Gill  AC, Sauer  MJ. High-resolution differentiation of transmissible spongiform encephalopathy strains by quantitative N-terminal amino acid profiling (N-TAAP) of PK-digested abnormal prion protein. J Mass Spectrom. 2009;44:38496. DOIPubMedGoogle Scholar
  4. Will  RG, Ironside  JW, Zeidler  M, Cousens  SN, Estibeiro  K, Alperovitch  A, et al. A new variant of Creutzfeldt-Jakob disease in the UK. Lancet. 1996;347:9215. DOIPubMedGoogle Scholar
  5. Wells  GA, Scott  AC, Johnson  CT, Gunning  RF, Hancock  RD, Jeffrey  M, et al. A novel progressive spongiform encephalopathy in cattle. Vet Rec. 1987;121:41920. DOIPubMedGoogle Scholar
  6. Fernández-Borges  N, Marín-Moreno  A, Konold  T, Espinosa  JC, Torres  JM. Bovine spongiform encephalopathy (BSE). In: Reference module in neuroscience and biobehavioral psychology. London: Elsevier; 2017. p.1–10.
  7. Houston  F, Andréoletti  O. Animal prion diseases: the risks to human health. Brain Pathol. 2019;29:24862. DOIPubMedGoogle Scholar
  8. Casalone  C, Zanusso  G, Acutis  P, Ferrari  S, Capucci  L, Tagliavini  F, et al. Identification of a second bovine amyloidotic spongiform encephalopathy: molecular similarities with sporadic Creutzfeldt-Jakob disease. Proc Natl Acad Sci U S A. 2004;101:306570. DOIPubMedGoogle Scholar
  9. Biacabe  AG, Laplanche  JL, Ryder  S, Baron  T. Distinct molecular phenotypes in bovine prion diseases. EMBO Rep. 2004;5:1105. DOIPubMedGoogle Scholar
  10. Béringue  V, Herzog  L, Reine  F, Le Dur  A, Casalone  C, Vilotte  JL, et al. Transmission of atypical bovine prions to mice transgenic for human prion protein. Emerg Infect Dis. 2008;14:1898901. DOIPubMedGoogle Scholar
  11. Eloit  M, Adjou  K, Coulpier  M, Fontaine  JJ, Hamel  R, Lilin  T, et al. BSE agent signatures in a goat. Vet Rec. 2005;156:5234. DOIPubMedGoogle Scholar
  12. Padilla  D, Béringue  V, Espinosa  JC, Andreoletti  O, Jaumain  E, Reine  F, et al. Sheep and goat BSE propagate more efficiently than cattle BSE in human PrP transgenic mice. PLoS Pathog. 2011;7:e1001319. DOIPubMedGoogle Scholar
  13. Simmons  MM, Chaplin  MJ, Konold  T, Casalone  C, Beck  KE, Thorne  L, et al. L-BSE experimentally transmitted to sheep presents as a unique disease phenotype. Vet Res (Faisalabad). 2016;47:112. DOIPubMedGoogle Scholar
  14. Béringue  V, Andréoletti  O, Le Dur  A, Essalmani  R, Vilotte  JL, Lacroux  C, et al. A bovine prion acquires an epidemic bovine spongiform encephalopathy strain-like phenotype on interspecies transmission. J Neurosci. 2007;27:696571. DOIPubMedGoogle Scholar
  15. Lloyd  SE, Mead  S, Collinge  J. Genetics of prion diseases. Curr Opin Genet Dev. 2013;23:34551. DOIPubMedGoogle Scholar
  16. Mok  T, Jaunmuktane  Z, Joiner  S, Campbell  T, Morgan  C, Wakerley  B, et al. Variant Creutzfeldt-Jakob disease in a patient with heterozygosity at PRNP codon 129. N Engl J Med. 2017;376:2924. DOIPubMedGoogle Scholar
  17. Will  RG, Zeidler  M, Stewart  GE, Macleod  MA, Ironside  JW, Cousens  SN, et al. Diagnosis of new variant Creutzfeldt-Jakob disease. Ann Neurol. 2000;47:57582. DOIPubMedGoogle Scholar
  18. Fernández-Borges  N, Espinosa  JC, Marín-Moreno  A, Aguilar-Calvo  P, Asante  EA, Kitamoto  T, et al. Val129-PrP variant is a strong molecular protector against BSE zoonotic transmission but fails to prevent human-to-human vCJD transmission. Emerg Infect Dis. 2017;23:152230.PubMedGoogle Scholar
  19. Le Dur  A, Béringue  V, Andréoletti  O, Reine  F, Laï  TL, Baron  T, et al. A newly identified type of scrapie agent can naturally infect sheep with resistant PrP genotypes. Proc Natl Acad Sci U S A. 2005;102:160316. DOIPubMedGoogle Scholar
  20. Kupfer  L, Eiden  M, Buschmann  A, Groschup  MH. Amino acid sequence and prion strain specific effects on the in vitro and in vivo convertibility of ovine/murine and bovine/murine prion protein chimeras. Biochim Biophys Acta. 2007;1772:70413. DOIPubMedGoogle Scholar
  21. Castilla  J, Gutiérrez Adán  A, Brun  A, Pintado  B, Ramírez  MA, Parra  B, et al. Early detection of PrPres in BSE-infected bovine PrP transgenic mice. Arch Virol. 2003;148:67791. DOIPubMedGoogle Scholar
  22. Andréoletti  O, Berthon  P, Levavasseur  E, Marc  D, Lantier  F, Monks  E, et al. Phenotyping of protein-prion (PrPsc)-accumulating cells in lymphoid and neural tissues of naturally scrapie-affected sheep by double-labeling immunohistochemistry. J Histochem Cytochem. 2002;50:135770. DOIPubMedGoogle Scholar
  23. Fraser  H, Dickinson  AG. The sequential development of the brain lesion of scrapie in three strains of mice. J Comp Pathol. 1968;78:30111. DOIPubMedGoogle Scholar
  24. Andréoletti  O, Simon  S, Lacroux  C, Morel  N, Tabouret  G, Chabert  A, et al. PrPSc accumulation in myocytes from sheep incubating natural scrapie. Nat Med. 2004;10:5913. DOIPubMedGoogle Scholar
  25. Féraudet  C, Morel  N, Simon  S, Volland  H, Frobert  Y, Créminon  C, et al. Screening of 145 anti-PrP monoclonal antibodies for their capacity to inhibit PrPSc replication in infected cells. J Biol Chem. 2005;280:1124758. DOIPubMedGoogle Scholar
  26. Cassard  H, Torres  JM, Lacroux  C, Douet  JY, Benestad  SL, Lantier  F, et al. Evidence for zoonotic potential of ovine scrapie prions. Nat Commun. 2014;5:5821. DOIPubMedGoogle Scholar
  27. Kong  Q, Zheng  M, Casalone  C, Qing  L, Huang  S, Chakraborty  B, et al. Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain. J Virol. 2008;82:3697701. DOIPubMedGoogle Scholar
  28. Wilson  R, Dobie  K, Hunter  N, Casalone  C, Baron  T, Barron  RM. Presence of subclinical infection in gene-targeted human prion protein transgenic mice exposed to atypical bovine spongiform encephalopathy. J Gen Virol. 2013;94:281927. DOIPubMedGoogle Scholar
  29. Wilson  R, Plinston  C, Hunter  N, Casalone  C, Corona  C, Tagliavini  F, et al. Chronic wasting disease and atypical forms of bovine spongiform encephalopathy and scrapie are not transmissible to mice expressing wild-type levels of human prion protein. J Gen Virol. 2012;93:16249. DOIPubMedGoogle Scholar
  30. Gill  ON, Spencer  Y, Richard-Loendt  A, Kelly  C, Dabaghian  R, Boyes  L, et al. Prevalent abnormal prion protein in human appendixes after bovine spongiform encephalopathy epizootic: large scale survey. BMJ. 2013;347(oct15 5):f5675. DOIPubMedGoogle Scholar
  31. Hilton  DA, Ghani  AC, Conyers  L, Edwards  P, McCardle  L, Ritchie  D, et al. Prevalence of lymphoreticular prion protein accumulation in UK tissue samples. J Pathol. 2004;203:7339. DOIPubMedGoogle Scholar
  32. Ironside  JW, Bishop  MT, Connolly  K, Hegazy  D, Lowrie  S, Le Grice  M, et al. Variant Creutzfeldt-Jakob disease: prion protein genotype analysis of positive appendix tissue samples from a retrospective prevalence study. BMJ. 2006;332:11868. DOIPubMedGoogle Scholar
  33. Le Dur  A, Laï  TL, Stinnakre  MG, Laisné  A, Chenais  N, Rakotobe  S, et al. Divergent prion strain evolution driven by PrPC expression level in transgenic mice. Nat Commun. 2017;8:14170. DOIPubMedGoogle Scholar

Main Article

1These first authors contributed equally to this article.

2Current affiliation: University of California–San Diego, La Jolla, California, USA.

Page created: May 18, 2020
Page updated: May 18, 2020
Page reviewed: May 18, 2020
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.