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

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...

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Autores principales: Götte, Dorothea R., Benestad, Sylvie L., Laude, Hubert, Zurbriggen, Andreas, Oevermann, Anna, Seuberlich, Torsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214077/
https://www.ncbi.nlm.nih.gov/pubmed/22096587
http://dx.doi.org/10.1371/journal.pone.0027510
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author Götte, Dorothea R.
Benestad, Sylvie L.
Laude, Hubert
Zurbriggen, Andreas
Oevermann, Anna
Seuberlich, Torsten
author_facet Götte, Dorothea R.
Benestad, Sylvie L.
Laude, Hubert
Zurbriggen, Andreas
Oevermann, Anna
Seuberlich, Torsten
author_sort Götte, Dorothea R.
collection PubMed
description 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.
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spelling pubmed-32140772011-11-17 Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature Götte, Dorothea R. Benestad, Sylvie L. Laude, Hubert Zurbriggen, Andreas Oevermann, Anna Seuberlich, Torsten PLoS One Research Article 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. Public Library of Science 2011-11-11 /pmc/articles/PMC3214077/ /pubmed/22096587 http://dx.doi.org/10.1371/journal.pone.0027510 Text en Götte et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Götte, Dorothea R.
Benestad, Sylvie L.
Laude, Hubert
Zurbriggen, Andreas
Oevermann, Anna
Seuberlich, Torsten
Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature
title Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature
title_full Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature
title_fullStr Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature
title_full_unstemmed Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature
title_short Atypical Scrapie Isolates Involve a Uniform Prion Species with a Complex Molecular Signature
title_sort atypical scrapie isolates involve a uniform prion species with a complex molecular signature
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3214077/
https://www.ncbi.nlm.nih.gov/pubmed/22096587
http://dx.doi.org/10.1371/journal.pone.0027510
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