title: Atypical scrapie isolates involve a uniform prion species with a complex molecular signature.
abstract: The pathobiology of atypical scrapie, a prion disease affecting sheep and goats, is still poorly understood. In a previous study, we demonstrated that atypical scrapie affecting small ruminants in Switzerland differs in the neuroanatomical distribution of the pathological prion protein (PrP(d)). To investigate whether these differences depend on host-related vs. pathogen-related factors, we transmitted atypical scrapie to transgenic mice over-expressing the ovine prion protein (tg338). The clinical, neuropathological, and molecular phenotype of tg338 mice is similar between mice carrying the Swiss atypical scrapie isolates and the Nor98, an atypical scrapie isolate from Norway. Together with published data, our results suggest that atypical scrapie is caused by a uniform type of prion, and that the observed phenotypic differences in small ruminants are likely host-dependant. Strikingly, by using a refined SDS-PAGE technique, we established that the prominent proteinase K-resistant prion protein fragment in atypical scrapie consists of two separate, unglycosylated peptides with molecular masses of roughly 5 and 8 kDa. These findings show similarities to those for other prion diseases in animals and humans, and lay the groundwork for future comparative research.
authors.affiliation: NeuroCentre, National and OIE Reference Laboratories for BSE and Scrapie, Division of Experimental Clinical Research, Vetsuisse Faculty, University of Berne, Berne, Switzerland.
authors.forename: Dorothea R
authors.initials: DR
authors.lastname: Götte
authors.forename: Sylvie L
authors.initials: SL
authors.lastname: Benestad
authors.forename: Hubert
authors.initials: H
authors.lastname: Laude
authors.forename: Andreas
authors.initials: A
authors.lastname: Zurbriggen
authors.forename: Anna
authors.initials: A
authors.lastname: Oevermann
authors.forename: Torsten
authors.initials: T
authors.lastname: Seuberlich
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D019286:Endopeptidase K / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D011328:Prions / Q000378:metabolism*; D012608:Scrapie / Q000378:metabolism*; D012756:Sheep
chemical_list: D011328:Prions; D019286:Endopeptidase K
references.citation: J Clin Invest. 2010 Jul;120(7):2590-9
references.pmid: 20551516
references.citation: Emerg Infect Dis. 2007 Aug;13(8):1201-7
references.pmid: 17953092
references.citation: Vet Res. 2007 Jan-Feb;38(1):65-80
references.pmid: 17156738
references.citation: Vet Rec. 2005 Apr 16;156(16):523-4
references.pmid: 15833975
references.citation: PLoS One. 2009 Oct 06;4(10):e7300
references.pmid: 19806224
references.citation: J Gen Virol. 2010 Oct;91(Pt 10):2630-41
references.pmid: 20538906
references.citation: J Gen Virol. 1991 Mar;72 ( Pt 3):595-603
references.pmid: 1672371
references.citation: Vet J. 2010 Sep;185(3):338-40
references.pmid: 19635675
references.citation: J Comp Pathol. 2006 Feb-Apr;134(2-3):171-81
references.pmid: 16542672
references.citation: BMC Vet Res. 2007 Aug 28;3:20
references.pmid: 17725818
references.citation: J Biol Chem. 1995 Aug 11;270(32):19173-80
references.pmid: 7642585
references.citation: Science. 1991 Jun 14;252(5012):1515-22
references.pmid: 1675487
references.citation: PLoS Pathog. 2007 Jun;3(6):e82
references.pmid: 17559305
references.citation: Vet Res. 2011 Feb 15;42:32
references.pmid: 21324114
references.citation: Emerg Infect Dis. 2011 May;17(5):848-54
references.pmid: 21529394
references.citation: J Biol Chem. 2003 Oct 17;278(42):40429-36
references.pmid: 12917418
references.citation: Vet Res. 2008 Jul-Aug;39(4):19
references.pmid: 18187032
references.citation: J Gen Virol. 2010 Aug;91(Pt 8):2132-2138
references.pmid: 20392900
references.citation: Nature. 1967 Sep 2;215(5105):1043-4
references.pmid: 4964084
references.citation: Proc Natl Acad Sci U S A. 2005 Nov 1;102(44):16031-6
references.pmid: 16239348
references.citation: C R Biol. 2002 Jan;325(1):49-57
references.pmid: 11862622
references.citation: Vet Rec. 2003 Aug 16;153(7):202-8
references.pmid: 12956297
references.citation: Acta Neuropathol. 2007 Aug;114(2):195-9
references.pmid: 17576581
references.citation: Vet Rec. 1993 Oct 2;133(14):339-41
references.pmid: 8236676
references.citation: Brain Res Bull. 2008 Dec 16;77(6):343-55
references.pmid: 18951958
references.citation: Emerg Infect Dis. 2007 Jan;13(1):58-65
references.pmid: 17370516
references.citation: J Gen Virol. 2006 Feb;87(Pt 2):471-477
references.pmid: 16432036
references.citation: BMC Vet Res. 2006 Jun 09;2:19
references.pmid: 16764717
references.citation: J Comp Pathol. 1968 Jul;78(3):301-11
references.pmid: 4970192
references.citation: Vet Rec. 2009 May 30;164(22):677-81
references.pmid: 19483208
references.citation: J Clin Microbiol. 2011 Aug;49(8):3026-8
references.pmid: 21677067
references.citation: BMC Vet Res. 2010 Mar 26;6:17
references.pmid: 20346155
references.citation: J Clin Microbiol. 2007 Jun;45(6):1821-9
references.pmid: 17442800
references.citation: PLoS Pathog. 2011 Feb 10;7(2):e1001285
references.pmid: 21347349
references.citation: J Clin Microbiol. 2011 Jun;49(6):2109-15
references.pmid: 21450953
references.citation: J Gen Virol. 2006 Dec;87(Pt 12):3715-3722
references.pmid: 17098989
references.citation: J Biol Chem. 2001 Feb 23;276(8):6009-15
references.pmid: 11087738
references.citation: J Gen Virol. 2006 Jun;87(Pt 6):1751-1760
references.pmid: 16690942
references.citation: EMBO J. 1986 Oct;5(10):2591-7
references.pmid: 3096712
references.citation: BMC Vet Res. 2010 Mar 10;6:14
references.pmid: 20219126