Cargando…

Seeded Fibrillation as Molecular Basis of the Species Barrier in Human Prion Diseases

Prion diseases are transmissible spongiform encephalopathies in humans and animals, including scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer, and Creutzfeldt-Jakob disease (CJD) in humans. The hallmark of prion diseases is the conversion of...

Descripción completa

Detalles Bibliográficos
Autores principales: Luers, Lars, Bannach, Oliver, Stöhr, Jan, Wördehoff, Michael Marius, Wolff, Martin, Nagel-Steger, Luitgard, Riesner, Detlev, Willbold, Dieter, Birkmann, Eva
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748051/
https://www.ncbi.nlm.nih.gov/pubmed/23977331
http://dx.doi.org/10.1371/journal.pone.0072623
_version_ 1782281024471826432
author Luers, Lars
Bannach, Oliver
Stöhr, Jan
Wördehoff, Michael Marius
Wolff, Martin
Nagel-Steger, Luitgard
Riesner, Detlev
Willbold, Dieter
Birkmann, Eva
author_facet Luers, Lars
Bannach, Oliver
Stöhr, Jan
Wördehoff, Michael Marius
Wolff, Martin
Nagel-Steger, Luitgard
Riesner, Detlev
Willbold, Dieter
Birkmann, Eva
author_sort Luers, Lars
collection PubMed
description Prion diseases are transmissible spongiform encephalopathies in humans and animals, including scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer, and Creutzfeldt-Jakob disease (CJD) in humans. The hallmark of prion diseases is the conversion of the host-encoded prion protein (PrP(C)) to its pathological isoform PrP(Sc), which is accompanied by PrP fibrillation. Transmission is not restricted within one species, but can also occur between species. In some cases a species barrier can be observed that results in limited or unsuccessful transmission. The mechanism behind interspecies transmissibility or species barriers is not completely understood. To analyse this process at a molecular level, we previously established an in vitro fibrillation assay, in which recombinant PrP (recPrP) as substrate can be specifically seeded by PrP(Sc) as seed. Seeding with purified components, with no additional cellular components, is a direct consequence of the “prion-protein-only” hypothesis. We therefore hypothesise, that the species barrier is based on the interaction of PrP(C) and PrP(Sc). Whereas in our earlier studies, the interspecies transmission in animal systems was analysed, the focus of this study lies on the transmission from animals to humans. We therefore combined seeds from species cattle, sheep and deer (BSE, scrapie, CWD) with human recPrP. Homologous seeding served as a control. Our results are consistent with epidemiology, other in vitro aggregation studies, and bioassays investigating the transmission between humans, cattle, sheep, and deer. In contrast to CJD and BSE seeds, which show a seeding activity we can demonstrate a species barrier for seeds from scrapie and CWD in vitro. We could show that the seeding activity and therewith the molecular interaction of PrP as substrate and PrP(Sc) as seed is sufficient to explain the phenomenon of species barriers. Therefore our data supports the hypothesis that CWD is not transmissible to humans.
format Online
Article
Text
id pubmed-3748051
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37480512013-08-23 Seeded Fibrillation as Molecular Basis of the Species Barrier in Human Prion Diseases Luers, Lars Bannach, Oliver Stöhr, Jan Wördehoff, Michael Marius Wolff, Martin Nagel-Steger, Luitgard Riesner, Detlev Willbold, Dieter Birkmann, Eva PLoS One Research Article Prion diseases are transmissible spongiform encephalopathies in humans and animals, including scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) in deer, and Creutzfeldt-Jakob disease (CJD) in humans. The hallmark of prion diseases is the conversion of the host-encoded prion protein (PrP(C)) to its pathological isoform PrP(Sc), which is accompanied by PrP fibrillation. Transmission is not restricted within one species, but can also occur between species. In some cases a species barrier can be observed that results in limited or unsuccessful transmission. The mechanism behind interspecies transmissibility or species barriers is not completely understood. To analyse this process at a molecular level, we previously established an in vitro fibrillation assay, in which recombinant PrP (recPrP) as substrate can be specifically seeded by PrP(Sc) as seed. Seeding with purified components, with no additional cellular components, is a direct consequence of the “prion-protein-only” hypothesis. We therefore hypothesise, that the species barrier is based on the interaction of PrP(C) and PrP(Sc). Whereas in our earlier studies, the interspecies transmission in animal systems was analysed, the focus of this study lies on the transmission from animals to humans. We therefore combined seeds from species cattle, sheep and deer (BSE, scrapie, CWD) with human recPrP. Homologous seeding served as a control. Our results are consistent with epidemiology, other in vitro aggregation studies, and bioassays investigating the transmission between humans, cattle, sheep, and deer. In contrast to CJD and BSE seeds, which show a seeding activity we can demonstrate a species barrier for seeds from scrapie and CWD in vitro. We could show that the seeding activity and therewith the molecular interaction of PrP as substrate and PrP(Sc) as seed is sufficient to explain the phenomenon of species barriers. Therefore our data supports the hypothesis that CWD is not transmissible to humans. Public Library of Science 2013-08-20 /pmc/articles/PMC3748051/ /pubmed/23977331 http://dx.doi.org/10.1371/journal.pone.0072623 Text en © 2013 Luers 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
Luers, Lars
Bannach, Oliver
Stöhr, Jan
Wördehoff, Michael Marius
Wolff, Martin
Nagel-Steger, Luitgard
Riesner, Detlev
Willbold, Dieter
Birkmann, Eva
Seeded Fibrillation as Molecular Basis of the Species Barrier in Human Prion Diseases
title Seeded Fibrillation as Molecular Basis of the Species Barrier in Human Prion Diseases
title_full Seeded Fibrillation as Molecular Basis of the Species Barrier in Human Prion Diseases
title_fullStr Seeded Fibrillation as Molecular Basis of the Species Barrier in Human Prion Diseases
title_full_unstemmed Seeded Fibrillation as Molecular Basis of the Species Barrier in Human Prion Diseases
title_short Seeded Fibrillation as Molecular Basis of the Species Barrier in Human Prion Diseases
title_sort seeded fibrillation as molecular basis of the species barrier in human prion diseases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748051/
https://www.ncbi.nlm.nih.gov/pubmed/23977331
http://dx.doi.org/10.1371/journal.pone.0072623
work_keys_str_mv AT luerslars seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases
AT bannacholiver seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases
AT stohrjan seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases
AT wordehoffmichaelmarius seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases
AT wolffmartin seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases
AT nagelstegerluitgard seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases
AT riesnerdetlev seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases
AT willbolddieter seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases
AT birkmanneva seededfibrillationasmolecularbasisofthespeciesbarrierinhumanpriondiseases