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Volume 20, Number 1—January 2014
Research

Molecular Barriers to Zoonotic Transmission of Prions

Marcelo A. Barria, Aru Balachandran, Masanori Morita, Tetsuyuki Kitamoto, Rona Barron, Jean Manson, Richard Knight, James W. Ironside, and Mark W. HeadComments to Author 
Author affiliations: The University of Edinburgh, Edinburgh, Scotland, UK (M.A. Barria, R. Knight, J.W. Ironside, M.W Head); Canadian Food Inspection Agency, Ottawa, Ontario, Canada (A. Balachandran); Japan Blood Products Organization, Kobe, Japan (M. Morita); Tohoku University Graduate School of Medicine, Sendai, Japan (T. Kitamoto); University of Edinburgh, Easter Bush, Scotland, UK (R. Barron, J. Manson)

Main Article

Table

Comparison of the outcomes of experimental transmission and in vitro conversion studies of chronic wasting disease in human, humanized, and nonhuman primate model systems*

Donor animal inoculum In vivo
In vitro
Ref
Species inoculated Animal (expression levels)/codon 129 Transmission PrP source (expression levels)/codon 129 Method Conversion
Mule deer, white-tailed deer, and elk


Cells 129M and 129V
C-FA
Pos
(28,29)
Elk
Humanized PrP transgenic mice
Tg-40 (1×)/129MM Neg

(24)
Tg-1 (2×)/129MM
Neg
Mule deer
Squirrel monkeys
Saimiri sciureus (1×)
Pos


(20)
Mule deer, white-tailed deer, and elk
Humanized PrP transgenic mice
Tg(HuPrP)440 (2×)
Neg


(27)
Mule deer, white-tailed deer, and elk
Squirrel monkeys Saimiri sciureus (1×) Pos

(22)
Cynomolgus macaques
Macaca fascicularis (1×)
Neg
Mule deer and white-tailed deer

Tg-6816 (16×)/129M PMCA Neg (31)

Tg-7823 (5×)/129V
PMCA
Neg
Mule deer
Humanized PrP transgenic mice
Tg-45 (4×)/129MM Neg
(26)
Tg-35 (2×)/129M Neg
Tg-152 (6×)/129VV
Neg

White-tailed deer
Humanized PrP transgenic mice
HuMM (1×)/129MM Neg

(11)
HuVV (1×)/129VV
Neg
Mule deer


Tg-440 (2×)/129MM
PMCA
Pos
(after in vitro conditioning)
(33)
Elk Human brain (1×)/129MM PMCA Pos This article
Human brain (1×)/129VV PMCA Pos
HuMM (1×)/129MM PMCA Pos
HuVV(1×)/129VV PMCA Pos
293F cell line(4×)/129M PMCA Pos
293F cell line(2×)/129V PMCA Pos

*Numbers in parentheses denote the stated expression levels of PrPc into the animal species and cell lines used. PrP, prion protein; C-FA, cell-free assay; pos, positive; neg, negative; PrPc, host’s normal cellular PrP. Blank cells indicate no reported data.

Main Article

References
  1. Benestad  SL, Sarradin  P, Thu  B, Schoenheit  J, Tanulis  MA, Bratberg  B. Cases of scrapie with unusual features in Norway and designation of a new type, Nor98. Vet Rec. 2003;153:2028. DOIPubMed
  2. Casalone  C, Zanusso  G, Acutis  P, Ferrari  S, Capucci  L, Tagliavini  F, 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. DOIPubMed
  3. Biacabe  AG, Laplanche  JL, Ryder  S, Baron  T. Distinct molecular phenotypes in bovine prion diseases. EMBO Rep. 2004;5:1105 . DOIPubMed
  4. Tranulis  MA, Benestad  SL, Baron  T, Kretzschmar  H. Atypical prion diseases in humans and animals. Top Curr Chem. 2011;305:2350. DOIPubMed
  5. Saunders  SE, Bartelt-Hunt  SL, Bartz  JC. Occurrence, transmission, and zoonotic potential of chronic wasting disease. Emerg Infect Dis. 2012;18:36976. DOIPubMed
  6. Le Dur  A, Beringue  V, Andreoletti  A, Reine  F, Lai  TL, Baron  T, 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. DOIPubMed
  7. Jacobs  JG, Langeveld  JP, Biacabe  AG, Acutis  PL, Polak  MP, Gavier-Widen  D, Molecular discrimination of atypical bovine spongiform encephalopathy strains from a geographical region spanning a wide area in Europe. J Clin Microbiol. 2007;45:18219 . DOIPubMed
  8. Castilla  J, Gonzalez-Romero  D, Saa  P, Morales  R, De Castro  J, Soto  C. Crossing the species barrier by PrP(Sc) replication in vitro generates unique infectious prions. Cell. 2008;134:75768. DOIPubMed
  9. Orrú  CD, Caughey  B. Prion seeded conversion and amplification assays. Top Curr Chem. 2011;305:12133 . DOIPubMed
  10. Jones  M, Wight  D, Barron  R, Jeffrey  M, Manson  J, Prowse  C, Molecular model of prion transmission to humans. Emerg Infect Dis. 2009;15:20136 . DOIPubMed
  11. Wilson  R, Plinston  C, Hunter  N, Casalone  C, Corona  C, Tagliavini  F, 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 . DOIPubMed
  12. 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 . DOIPubMed
  13. Plinston  C, Hart  P, Chong  A, Hunter  N, Foster  J, Piccardo  P, Increased susceptibility of human-PrP transgenic mice to bovine spongiform encephalopathy infection following passage in sheep. J Virol. 2011;85:117481. DOIPubMed
  14. Yokoyama  T, Takeuchi  A, Yamamoto  M, Kitamoto  T, Ironside  JW, Morita  M. Heparin enhances the cell-protein misfolding cyclic amplification efficiency of variant Creutzfeldt-Jakob disease. Neurosci Lett. 2011;498:11923. DOIPubMed
  15. Saá  P, Castilla  J, Soto  C. Cyclic amplification of protein misfolding and aggregation. Methods Mol Biol. 2005;299:5365 .PubMed
  16. Barria  MA, Gonzalez-Romero  D, Soto  C. Cyclic amplification of prion protein misfolding. Methods Mol Biol. 2012;849:199212. DOIPubMed
  17. Jones  M, Peden  AHMW, Ironside  JW. The application of in vitro cell-free conversion systems to human prion diseases. Acta Neuropathol. 2011;121:13543 . DOIPubMed
  18. Gambetti  P, Cali  I, Notari  S, Kong  Q, Zou  WQ, Surewicz  WK. Molecular biology and pathology of prion strains in sporadic human prion diseases. Acta Neuropathol. 2011;121:7990. DOIPubMed
  19. Collinge  J, Clarke  AR. A general model of prion strains and their pathogenicity. Science. 2007;318:9306. DOIPubMed
  20. Marsh  RF, Kincaid  AE, Bessen  RA, Bartz  JC. Interspecies transmission of chronic wasting disease prions to squirrel monkeys (Saimiti sciureus). J Virol. 2005;79:137946. DOIPubMed
  21. Comoy  EE, Casalone  C, Lescoutra-Etchegaray  N, Zanusso  G, Freire  S, Marce  D, Atypical BSE (BASE) transmitted from asymptomatic aging aattle to a primate. PLoS ONE. 2008;3:e3017. DOIPubMed
  22. Race  B, Meade-White  KD, Miller  MW, Barbian  KD, Rubenstein  R, LaFauci  G, Susceptibilities of nonhuman primates to chronic wasting disease. Emerg Infect Dis. 2009;15:136676. DOIPubMed
  23. Ono  F, Tase  N, Kurosawa  A, Hiyaoka  A, Ohyama  A, Tezuka  Y, Atypical L-type bovine spongiform encephalopathy (L-BSE) transmission to cynomolgus macaques, a non-human primate. Jpn J Infect Dis. 2011;64:814 .PubMed
  24. 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. DOIPubMed
  25. Béringue  V, Herzog  L, Reine  F, Le Dur  A, Casalone  C, Vilotte  JL, Transmission of atypical bovine prions to mice transgenic for human prion protein. Emerg Infect Dis. 2008;14:1898901. DOIPubMed
  26. 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. DOIPubMed
  27. Tamgüney  G, Giles  K, Oehler  A, Johnson  NL, DeArmond  SJ, Prusiner  SB. Transmission of elk and deer prions to transgenic mice. J Virol. 2006;80:910414. DOIPubMed
  28. Raymond  GJ, Hope  J, Kocisko  DA, Priola  SA, Raymond  LD, Brossers  A, Molecular assessment of the potential transmissibilities of BSE and scrapie to humans. Nature. 1997;388:2858. DOIPubMed
  29. Raymond  GJ, Bossers  A, Raymond  DL, O’Rourke  KI, McHolland  LE, Bryant  PK, Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease. EMBO J. 2000;19:442530. DOIPubMed
  30. Castilla  J, Morales  R, Saá  P, Barria  M, Gambetti  P, Soto  C. Cell-free propagation of prion strains. EMBO J. 2008;27:255766. DOIPubMed
  31. Kurt  TD, Telling  GC, Zabel  MD, Hoover  EA. Trans-species amplification of Prp(CWD) and correlation with rigid loop 170N. Virology. 2009;387:23543. DOIPubMed
  32. Green  KM, Castilla  J, Seward  TS, Napier  DL, Jewell  JE, Soto  C, Accelerated high fidelity amplification within and across prion species barriers. PLoS Pathog. 2008;4:e1000139. DOIPubMed
  33. Barria  MA, Telling  GC, Gambetti  P, Mastrianni  JA, Soto  C. Generation of a novel form of human PrP(Sc) by inter-species transmission from cervid prions. J Biol Chem. 2011;286:74905. DOIPubMed
  34. Angers  RC, Kang  HE, Napier  D, Browning  S, Seward  T, Mathiason  C, Prion strain mutation determined by prion protein conformational compatibility and primary structure. Science. 2010;328:11548. DOIPubMed
  35. Perrott  MR, Sigurdson  CJ, Mason  GL, Hoover  EA. Evidence for distinct chronic wasting disease (CWD) strains in experimental CWD in ferrets. J Gen Virol. 2012;93:21221. DOIPubMed
  36. Telling  GC. Chronic wasting disease and the development of research models. In: Zou WQ, Gambetti P, editors. Prions and diseases. Volume 2. Animals, humans and the environment. New York: Springer; 2013. p. 45–56.
  37. Meyerett  C, Michel  B, Pulford  B, Spraker  TR, Nichols  TA, Johnson  T, In vitro strain adaptation of CWD prions by serial protein misfolding cyclic amplification. Virology. 2008;382:26776. DOIPubMed
  38. 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. DOIPubMed
  39. Wilson  R, King  D, Hunter  N, Goldmann  W, Barron  RM. Characterisation of an unusual transmissible spongiform encephalopathy in goat by transmission to knock-in transgenic mice. J Gen Virol. 2013;94:192232. DOIPubMed
  40. Thorne  L, Holder  T, Ramsay  A, Edwards  J, Taema  MM, Windl  O, In vitro amplification of ovine prions from scrapie-infected sheep from Great Britain reveals distinct patterns of propagation. BMC Vet Res. 2012;8:223. DOIPubMed

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Page created: January 03, 2014
Page updated: January 03, 2014
Page reviewed: January 03, 2014
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.
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