Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS

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Inherited prion disease (IPD) is caused by pathogenic mutations in the human prion protein (PrP) gene leading to the formation of lethal prions in the brain. To-date the properties of prions causing IPD and their similarities to prions causing other forms of human prion disease remain ill-defined. In the present study we have investigated the properties of prions seen in patients with Gerstmann-Sträussler-Scheinker (GSS) disease associated with the substitution of leucine for proline at amino acid position 102 (GSS P102L). We examined the ability of these prions to infect transgenic mice expressing human mutant 102L PrP, human wild-type PrP or wild-type mice. We found that GSS-102L prions have properties distinct from other types of human prions by showing that they can only infect transgenic mice expressing human PrP carrying the same mutation. Mice expressing wild-type human PrP or wild-type mouse PrP were entirely resistant to infection with GSS-102L prions. We conclude that accurate modeling of inherited prion disease requires the expression of authentic mutant human PrP in transgenic models, as other approaches may generate results that do not mirror the human disease.

Vyšlo v časopise: Transmission Properties of Human PrP 102L Prions Challenge the Relevance of Mouse Models of GSS. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1004953
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004953

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Zdroje

1. Prusiner SB (1998) Prions. Proc Natl Acad Sci USA 95 : 13363–13383. 9811807

2. Collinge J, Clarke A (2007) A general model of prion strains and their pathogenicity. Science 318 : 930–936. 17991853

3. Wadsworth JD, Asante EA, Collinge J (2010) Contribution of transgenic models to understanding human prion disease. Neuropathol Appl Neurobiol 36 : 576–597. doi: 10.1111/j.1365-2990.2010.01129.x 20880036

4. Collinge J (2005) Molecular neurology of prion disease. J Neurol Neurosurg Psychiatry 76 : 906–919. 15965195

5. Wadsworth JD, Collinge J (2011) Molecular pathology of human prion disease. Acta Neuropathol 121 : 69–77. doi: 10.1007/s00401-010-0735-5 20694796

6. Griffith JS (1967) Self replication and scrapie. Nature 215 : 1043–1044. 4964084

7. Prusiner SB (1982) Novel proteinaceous infectious particles cause scrapie. Science 216 : 136–144. 6801762

8. Caughey B, Baron GS (2006) Prions and their partners in crime. Nature 443 : 803–810. 17051207

9. Safar J, Wille H, Itri V, Groth D, Serban H et al. (1998) Eight prion strains have PrPSc molecules with different conformations. Nat Med 4 : 1157–1165. 9771749

10. Safar JG, Geschwind MD, Deering C, Didorenko S, Sattavat M et al. (2005) Diagnosis of human prion disease. Proc Natl Acad Sci USA 102 : 3501–3506. 15741275

11. Cronier S, Gros N, Tattum MH, Jackson GS, Clarke AR et al. (2008) Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysin. Biochem J 416 : 297–305. doi: 10.1042/BJ20081235 18684106

12. Sandberg MK, Al Doujaily H, Sharps B, Clarke AR, Collinge J (2011) Prion propagation and toxicity in vivo occur in two distinct mechanistic phases. Nature 470 : 540–542. doi: 10.1038/nature09768 21350487

13. Sandberg MK, Al Doujaily H, Sharps B, De Oliveira MW, Schmidt C et al. (2014) Prion neuropathology follows the accumulation of alternate prion protein isoforms after infective titre has peaked. Nat Commun 5 : 4347. doi: 10.1038/ncomms5347 25005024

14. Beck JA, Poulter M, Campbell TA, Adamson G, Uphill JB et al. (2010) PRNP allelic series from 19 years of prion protein gene sequencing at the MRC Prion Unit. Hum Mutat 31: E1551–E1563. doi: 10.1002/humu.21281 20583301

15. Hsiao K, Baker HF, Crow TJ, Poulter M, Owen F et al. (1989) Linkage of a prion protein missense variant to Gerstmann-Straussler syndrome. Nature 338 : 342–345. 2564168

16. Kovacs GG, Trabattoni G, Hainfellner JA, Ironside JW, Knight RS et al. (2002) Mutations of the prion protein gene phenotypic spectrum. J Neurol 249 : 1567–1582. 12420099

17. Kretzschmar HA, Honold G, Seitelberger F, Feucht M, Wessely P et al. (1991) Prion protein mutation in family first reported by Gerstmann, Straussler, and Scheinker. Lancet 337 : 1160. 1674033

18. Hainfellner JA, Brantner-Inthaler S, Cervenáková L, Brown P, Kitamoto T et al. (1995) The original Gerstmann-Straussler-Scheinker family of Austria: Divergent clinicopathological phenotypes but constant PrP genotype. Brain Pathol 5 : 201–211. 8520719

19. Kretzschmar HA, Kufer P, Riethmuller G, DeArmond SJ, Prusiner SB et al. (1992) Prion protein mutation at codon 102 in an Italian family with Gerstmann-Straussler-Scheinker syndrome. Neurology 42 : 809–810. 1348851

20. Barbanti P, Fabbrini G, Salvatore M, Petraroli R, Cardone F et al. (1996) Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity in a previously unreported family with Gerstmann-Straussler-Scheinker disease (PrP-P102L mutation). Neurology 47 : 734–741. 8797472

21. Piccardo P, Dlouhy SR, Lievens PMJ, Young K, Bird TD et al. (1998) Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity. J Neuropathol Exp Neurol 57 : 979–988. 9786248

22. Parchi P, Chen SG, Brown P, Zou W, Capellari S et al. (1998) Different patterns of truncated prion protein fragments correlate with distinct phenotypes in P102L Gerstmann-Sträussler-Scheinker disease. Proc Natl Acad Sci USA 95 : 8322–8327. 9653185

23. Majtenyi C, Brown P, Cervenakova L, Goldfarb LG, Tateishi J (2000) A three-sister sibship of Gerstmann-Straussler-Scheinker disease with a CJD phenotype. Neurology 54 : 2133–2137. 10851377

24. Wadsworth JD, Joiner S, Linehan J, Cooper S, Powell C et al. (2006) Phenotypic heterogeneity in inherited prion disease (P102L) is associated with differential propagation of protease-resistant wild-type and mutant prion protein. Brain 129 : 1557–1569. 16597650

25. Piccardo P, Manson JC, King D, Ghetti B, Barron RM (2007) Accumulation of prion protein in the brain that is not associated with transmissible disease. Proc Natl Acad Sci USA 104 : 4712–4717. 17360589

26. Webb TE, Poulter M, Beck J, Uphill J, Adamson G et al. (2008) Phenotypic heterogeneity and genetic modification of P102L inherited prion disease in an international series. Brain 131 : 2632–2646. doi: 10.1093/brain/awn202 18757886

27. Monaco S, Fiorini M, Farinazzo A, Ferrari S, Gelati M et al. (2012) Allelic origin of protease-sensitive and protease-resistant prion protein isoforms in Gerstmann-Straussler-Scheinker disease with the P102L mutation. PLoS ONE 7: e32382. doi: 10.1371/journal.pone.0032382 22384235

28. Popova SN, Tarvainen I, Capellari S, Parchi P, Hannikainen P et al. (2012) Divergent clinical and neuropathological phenotype in a Gerstmann-Straussler-Scheinker P102L family. Acta Neurol Scand 126 : 315–323. doi: 10.1111/j.1600-0404.2011.01628.x 22211828

29. Rusina R, Fiala J, Holada K, Matejckova M, Novakova J et al. (2012) Gerstmann-Straussler-Scheinker syndrome with the P102L pathogenic mutation presenting as familial Creutzfeldt-Jakob disease: a case report and review of the literature. Neurocase 19 : 41–53. doi: 10.1080/13554794.2011.654215 22494260

30. Riudavets MA, Sraka MA, Schultz M, Rojas E, Martinetto H et al. (2013) Gerstmann-Straussler-Scheinker syndrome with variable phenotype in a new kindred with PRNP-P102L mutation. Brain Pathol 24 : 142–147. doi: 10.1111/bpa.12083 23944754

31. Hill AF, Joiner S, Beck J, Campbell TA, Dickinson A et al. (2006) Distinct glycoform ratios of protease resistant prion protein associated with PRNP point mutations. Brain 129 : 676–685. 16415305

32. Collinge J (1999) Variant Creutzfeldt-Jakob disease. Lancet 354 : 317–323. 10440324

33. Asante EA, Gowland I, Grimshaw A, Linehan JM, Smidak M et al. (2009) Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins. J Gen Virol 90 : 546–558. doi: 10.1099/vir.0.007930-0 19218199

34. Hart T, Hosszu LL, Trevitt CR, Jackson GS, Waltho JP et al. (2009) Folding kinetics of the human prion protein probed by temperature jump. Proc Natl Acad Sci USA 106 : 5651–5656. doi: 10.1073/pnas.0811457106 19321423

35. Wadsworth JD, Asante EA, Desbruslais M, Linehan J, Joiner S et al. (2004) Human prion protein with valine 129 prevents expression of variant CJD phenotype. Science 306 : 1793–1796. 15539564

36. Manson JC, Jamieson E, Baybutt H, Tuzi NL, Barron R et al. (1999) A single amino acid alteration (101L) introduced into murine PrP dramatically alters incubation time of transmissible spongiform encephalopathy. EMBO J 18 : 6855–6864. 10581259

37. Collinge J, Palmer MS, Sidle KCL, Hill AF, Gowland I et al. (1995) Unaltered susceptibility to BSE in transgenic mice expressing human prion protein. Nature 378 : 779–783. 8524411

38. Collinge J, Sidle KC, Meads J, Ironside J, Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of 'new variant' CJD. Nature 383 : 685–690. 8878476

39. Hill AF, Desbruslais M, Joiner S, Sidle KCL, Gowland I et al. (1997) The same prion strain causes vCJD and BSE. Nature 389 : 448–450. 9333232

40. Telling GC, Scott M, Mastrianni J, Gabizon R, Torchia M et al. (1995) Prion propagation in mice expressing human and chimeric PrP transgenes implicates the interaction of cellular PrP with another protein. Cell 83 : 79–90. 7553876

41. Korth C, Kaneko K, Groth D, Heye N, Telling G et al. (2003) Abbreviated incubation times for human prions in mice expressing a chimeric mouse-human prion protein transgene. Proc Natl Acad Sci USA 100 : 4784–4789. 12684540

42. Wadsworth JD, Joiner S, Linehan JM, Desbruslais M, Fox K et al. (2008) Kuru prions and sporadic Creutzfeldt-Jakob disease prions have equivalent transmission properties in transgenic and wild-type mice. Proc Natl Acad Sci USA 105 : 3885–3890. doi: 10.1073/pnas.0800190105 18316717

43. Kobayashi A, Asano M, Mohri S, Kitamoto T (2007) Cross-sequence transmission of sporadic Creutzfeldt-Jakob disease creates a new prion strain. J Biol Chem 282 : 30022–30028. 17709374

44. Asante EA, Linehan J, Desbruslais M, Joiner S, Gowland I et al. (2002) BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 21 : 6358–6366. 12456643

45. Beringue V, Le Dur A, Tixador P, Reine F, Lepourry L et al. (2008) Prominent and persistent extraneural infection in human PrP transgenic mice infected with variant CJD. PLoS ONE 3: e1419. doi: 10.1371/journal.pone.0001419 18183299

46. Kong Q, Zheng M, Casalone C, Qing L, Huang S et al. (2008) Evaluation of the human transmission risk of an atypical bovine spongiform encephalopathy prion strain. J Virol 82 : 3697–3701. doi: 10.1128/JVI.02561-07 18234793

47. Telling GC, Scott M, Hsiao KK, Foster D, Yang S-L et al. (1994) Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. Proc Natl Acad Sci USA 91 : 9936–9940. 7937921

48. Li J, Browning S, Mahal SP, Oelschlegel AM, Weissmann C (2010) Darwinian evolution of prions in cell culture. Science 327 : 869–872. doi: 10.1126/science.1183218 20044542

49. Collinge J (2010) Medicine. Prion strain mutation and selection. Science 328 : 1111–1112. doi: 10.1126/science.1190815 20508117

50. Browning S, Baker CA, Smith E, Mahal SP, Herva ME et al. (2011) Abrogation of complex glycosylation by Swainsonine results in strain -⁠ and cell-specific inhibition of prion replication. J Biol Chem 286 : 40962–73. doi: 10.1074/jbc.M111.283978 21930694

51. Gabizon R, Telling G, Meiner Z, Halimi M, Kahana I et al. (1996) Insoluble wild-type and protease-resistant mutant prion protein in brains of patients with inherited prion disease. Nat Med 2 : 59–64. 8564843

52. Chen SG, Parchi P, Brown P, Capellari S, Zou WQ et al. (1997) Allelic origin of the abnormal prion protein isoform in familial prion diseases. Nat Med 3 : 1009–1015. 9288728

53. Silvestrini MC, Cardone F, Maras B, Pucci P, Barra D et al. (1997) Identification of the prion protein allotypes which accumulate in the brain of sporadic and familial Creutzfeldt-Jakob disease patients. Nat Med 3 : 521–525. 9142120

54. Capellari S, Cardone F, Notari S, Schinina ME, Maras B et al. (2005) Creutzfeldt-Jakob disease associated with the R208H mutation in the prion protein gene. Neurology 64 : 905–907. 15753435

55. Xiao X, Cali I, Dong Z, Puoti G, Yuan J et al. (2013) Protease-sensitive prions with 144-bp insertion mutations. Aging (Albany NY) 5 : 155–173. 23515139

56. Cardone F, Principe S, Schinina ME, Maras B, Capellari S et al. (2014) Mutant PrP(CJD) prevails over wild-type PrP(CJD) in the brain of V210I and R208H genetic Creutzfeldt-Jakob disease patients. Biochem Biophys Res Commun 454 : 289–294. doi: 10.1016/j.bbrc.2014.10.051 25450391

57. Asante EA, Li YG, Gowland I, Jefferys JG, Collinge J (2004) Pathogenic human prion protein rescues PrP null phenotype in transgenic mice. Neurosci Lett 360 : 33–36. 15082172

58. Khalili-Shirazi A, Quaratino S, Londei M, Summers L, Tayebi M et al. (2005) Protein conformation significantly influences immune responses to prion protein. J Immunol 174 : 3256–3263. 15749856

59. Khalili-Shirazi A, Summers L, Linehan J, Mallinson G, Anstee D et al. (2005) PrP glycoforms are associated in a strain-specific ratio in native PrPSc. J Gen Virol 86 : 2635–2644. 16099923

60. Wadsworth JD, Joiner S, Hill AF, Campbell TA, Desbruslais M et al. (2001) Tissue distribution of protease resistant prion protein in variant CJD using a highly sensitive immuno-blotting assay. Lancet 358 : 171–180. 11476832

61. Wadsworth JD, Powell C, Beck JA, Joiner S, Linehan JM et al. (2008) Molecular diagnosis of human prion disease. Methods Mol Biol 459 : 197–227. doi: 10.1007/978-1-59745-234-2_14 18576157