Sunday, November 13, 2011

Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature

Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature

Dorothea R. Götte1, Sylvie L. Benestad2, Hubert Laude3, Andreas Zurbriggen1, Anna Oevermann1#, Torsten Seuberlich1#*

1 NeuroCentre, National and OIE Reference Laboratories for BSE and Scrapie, Division of Experimental Clinical Research, Vetsuisse Faculty, University of Berne, Berne, Switzerland, 2 Department of Pathology, Norwegian Veterinary Institute, Oslo, Norway, 3 3U892 Virologie Immunologie Moléculaires, Institut National de la Recherche Agronomique, Jouy-en-Josas, France

Abstract Top

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 (PrPd). 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.


Recently, we reported on a classical scrapie outbreak in a Greek goat flock, in which several animals exhibited a distinct C- and N-terminally ragged PK-resistant PrPres fragment [31]. This peptide demonstrated the same antibody-binding properties, and was estimated to be at similar molecular mass as the 5 kDa PrPres moiety described in the present study. At that time, it was unclear as to which type of prion disease this peptide was related. Our current findings support the idea that this fragment is related to atypical vs. classical scrapie, and that both prion species were present in the Greek flock. Future studies will conduct a direct comparison of these peptides by gradient SDS-PAGE, pending the receipt of material from mouse transmission studies of the Greek isolates.

PrPres peptides of low molecular mass have also been described in other types of prion disease, such as Gerstmann-Sträussler-Scheinker disease [32], [33] and Creutzfeldt-Jakob disease [34], [35] in humans as well as in H-BSE in cattle [36], [37]. Forthcoming directions of research are likely to focus on more precise comparative analyses of truncated PrPres peptides and their role in the biology of human and animal prion diseases...

Citation: Götte DR, Benestad SL, Laude H, Zurbriggen A, Oevermann A, et al. (2011) Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature. PLoS ONE 6(11): e27510. doi:10.1371/journal.pone.0027510

Editor: Jason Bartz, Creighton University, United States of America

Received: August 3, 2011; Accepted: October 18, 2011; Published: November 11, 2011

Copyright: © 2011 Götte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: This study was funded by the Swiss Federal Veterinary Office (grant #1.08.13.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail:

# These authors contributed equally to this work.

see full text ;


Molecular Features of the Protease-resistant Prion Protein (PrPres) in H-type BSE

Biacabe, A-G1; Jacobs, JG2; Gavier-Widén, D3; Vulin, J1; Langeveld, JPM2; Baron, TGM1 1AFSSA, France; 2CIDC-Lelystad, Netherlands; 3SVA, Sweden

Western blot analyses of PrPres accumulating in the brain of BSE-infected cattle have demonstrated 3 different molecular phenotypes regarding to the apparent molecular masses and glycoform ratios of PrPres bands. We initially described isolates (H-type BSE) essentially characterized by higher PrPres molecular mass and decreased levels of the diglycosylated PrPres band, in contrast to the classical type of BSE. This type is also distinct from another BSE phenotype named L-type BSE, or also BASE (for Bovine Amyloid Spongiform Encephalopathy), mainly characterized by a low representation of the diglycosylated PrPres band as well as a lower PrPres molecular mass. Retrospective molecular studies in France of all available BSE cases older than 8 years old and of part of the other cases identified since the beginning of the exhaustive surveillance of the disease in 20001 allowed to identify 7 H-type BSE cases, among 594 BSE cases that could be classified as classical, L- or H-type BSE. By Western blot analysis of H-type PrPres, we described a remarkable specific feature with antibodies raised against the C-terminal region of PrP that demonstrated the existence of a more C-terminal cleaved form of PrPres (named PrPres#2 ), in addition to the usual PrPres form (PrPres #1). In the unglycosylated form, PrPres #2 migrates at about 14 kDa, compared to 20 kDa for PrPres #1. The proportion of the PrPres#2 in cattle seems to by higher compared to the PrPres#1. Furthermore another PK-resistant fragment at about 7 kDa was detected by some more N-terminal antibodies and presumed to be the result of cleavages of both N- and C-terminal parts of PrP. These singular features were maintained after transmission of the disease to C57Bl/6 mice. The identification of these two additional PrPres fragments (PrPres #2 and 7kDa band) reminds features reported respectively in sporadic Creutzfeldt-Jakob disease and in Gerstmann-Sträussler-Scheinker (GSS) syndrome in humans.

Sunday, November 13, 2011

Microarray analysis in caudal medulla of cattle orally challenged with bovine spongiform encephalopathy

Wednesday, November 09, 2011

Case report Sporadic fatal insomnia in a young woman: A diagnostic challenge: Case Report TEXAS



Tuesday, November 08, 2011

Can Mortality Data Provide Reliable Indicators for Creutzfeldt-Jakob Disease Surveillance? A Study in France from 2000 to 2008 Vol. 37, No. 3-4, 2011

Original Paper

Conclusions:These findings raise doubt about the possibility of a reliable CJD surveillance only based on mortality data.

Thursday, July 14, 2011

Histopathological Studies of "CH1641-Like" Scrapie Sources Versus Classical Scrapie and BSE Transmitted to Ovine Transgenic Mice (TgOvPrP4)

Monday, June 27, 2011

Comparison of Sheep Nor98 with Human Variably Protease-Sensitive Prionopathy and Gerstmann-Sträussler-Scheinker Disease

Thursday, June 23, 2011

Experimental H-type bovine spongiform encephalopathy characterized by plaques and glial- and stellate-type prion protein deposits

Monday, June 20, 2011 2011

Annual Conference of the National Institute for Animal Agriculture ATYPICAL NOR-98 LIKE SCRAPIE UPDATE USA

Thursday, June 2, 2011

USDA scrapie report for April 2011 NEW ATYPICAL NOR-98 SCRAPIE CASES Pennsylvania AND California

Thursday, July 21, 2011

A Second Case of Gerstmann-Sträussler-Scheinker Disease Linked to the G131V Mutation in the Prion Protein Gene in a Dutch Patient Journal of Neuropathology & Experimental Neurology:

August 2011 - Volume 70 - Issue 8 - pp 698-702

Wednesday, February 16, 2011




Sunday, April 18, 2010


Monday, April 25, 2011

Experimental Oral Transmission of Atypical Scrapie to Sheep

Volume 17, Number 5-May 2011

Saturday, March 5, 2011


Thursday, August 4, 2011

Terry Singeltary Sr. on the Creutzfeldt-Jakob Disease Public Health Crisis, Date aired: 27 Jun 2011

Sunday, September 25, 2011

Mad Cow Scaremongers

Mad Cow Scaremongers by Terry S. Singeltary Sr. a review of the TSE prion agent 2003-2011

Monday, October 10, 2011

EFSA Journal 2011 The European Response to BSE: A Success Story


EFSA and the European Centre for Disease Prevention and Control (ECDC) recently delivered a scientific opinion on any possible epidemiological or molecular association between TSEs in animals and humans (EFSA Panel on Biological Hazards (BIOHAZ) and ECDC, 2011). This opinion confirmed Classical BSE prions as the only TSE agents demonstrated to be zoonotic so far but the possibility that a small proportion of human cases so far classified as "sporadic" CJD are of zoonotic origin could not be excluded. Moreover, transmission experiments to non-human primates suggest that some TSE agents in addition to Classical BSE prions in cattle (namely L-type Atypical BSE, Classical BSE in sheep, transmissible mink encephalopathy (TME) and chronic wasting disease (CWD) agents) might have zoonotic potential.


see follow-up here about North America BSE Mad Cow TSE prion risk factors, and the ever emerging strains of Transmissible Spongiform Encephalopathy in many species here in the USA, including humans ;



Terry S. Singeltary Sr. P.O. Box 42 Bacliff, Texas USA 77518

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