Molecular Modeling of Prion Transmission to Humans
Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA) to model int...
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doaj-9c58f6951438455d8d0eacd3b54c1b092020-11-24T23:13:51ZengMDPI AGViruses1999-49152014-10-016103766377710.3390/v6103766v6103766Molecular Modeling of Prion Transmission to HumansEtienne Levavasseur0Nicolas Privat1Juan-Carlos Espinosa Martin2Steve Simoneau3Thierry Baron4Benoit Flan5Juan-Maria Torres6Stéphane Haïk7Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ. Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, FranceInserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ. Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, FranceCentro de Investigacion en Sanidad Animal, Carretera de Algete a El Casar, 28130 Madrid, SpainLFB Biomédicaments, 91958 Les Ulis, FranceAgence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité Maladies neurodégénératives, 69394 Lyon, FranceLFB Biomédicaments, 91958 Les Ulis, FranceCentro de Investigacion en Sanidad Animal, Carretera de Algete a El Casar, 28130 Madrid, SpainInserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ. Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, 75013 Paris, FranceUsing different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA) to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains.http://www.mdpi.com/1999-4915/6/10/3766PrionProtein misfolding cyclic amplificationmolecular modelinterspecies barrier |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Etienne Levavasseur Nicolas Privat Juan-Carlos Espinosa Martin Steve Simoneau Thierry Baron Benoit Flan Juan-Maria Torres Stéphane Haïk |
spellingShingle |
Etienne Levavasseur Nicolas Privat Juan-Carlos Espinosa Martin Steve Simoneau Thierry Baron Benoit Flan Juan-Maria Torres Stéphane Haïk Molecular Modeling of Prion Transmission to Humans Viruses Prion Protein misfolding cyclic amplification molecular model interspecies barrier |
author_facet |
Etienne Levavasseur Nicolas Privat Juan-Carlos Espinosa Martin Steve Simoneau Thierry Baron Benoit Flan Juan-Maria Torres Stéphane Haïk |
author_sort |
Etienne Levavasseur |
title |
Molecular Modeling of Prion Transmission to Humans |
title_short |
Molecular Modeling of Prion Transmission to Humans |
title_full |
Molecular Modeling of Prion Transmission to Humans |
title_fullStr |
Molecular Modeling of Prion Transmission to Humans |
title_full_unstemmed |
Molecular Modeling of Prion Transmission to Humans |
title_sort |
molecular modeling of prion transmission to humans |
publisher |
MDPI AG |
series |
Viruses |
issn |
1999-4915 |
publishDate |
2014-10-01 |
description |
Using different prion strains, such as the variant Creutzfeldt-Jakob disease agent and the atypical bovine spongiform encephalopathy agents, and using transgenic mice expressing human or bovine prion protein, we assessed the reliability of protein misfolding cyclic amplification (PMCA) to model interspecies and genetic barriers to prion transmission. We compared our PMCA results with in vivo transmission data characterized by attack rates, i.e., the percentage of inoculated mice that developed the disease. Using 19 seed/substrate combinations, we observed that a significant PMCA amplification was only obtained when the mouse line used as substrate is susceptible to the corresponding strain. Our results suggest that PMCA provides a useful tool to study genetic barriers to transmission and to study the zoonotic potential of emerging prion strains. |
topic |
Prion Protein misfolding cyclic amplification molecular model interspecies barrier |
url |
http://www.mdpi.com/1999-4915/6/10/3766 |
work_keys_str_mv |
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