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Open AccessArticle

Molecular Modeling of Prion Transmission to Humans

1
Inserm 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, France
2
Centro de Investigacion en Sanidad Animal, Carretera de Algete a El Casar, 28130 Madrid, Spain
3
LFB Biomédicaments, 91958 Les Ulis, France
4
Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité Maladies neurodégénératives, 69394 Lyon, France
5
AP-HP, Hôpital de la Pitié-Salpêtrière, Cellule nationale de référence des MCJ, F-75013 Paris, France
6
AP-HP, Hôpital de la Pitié-Salpêtrière, Neuropathologie, 75013 Paris, France
*
Author to whom correspondence should be addressed.
Viruses 2014, 6(10), 3766-3777; https://doi.org/10.3390/v6103766
Received: 24 July 2014 / Revised: 26 September 2014 / Accepted: 30 September 2014 / Published: 2 October 2014
(This article belongs to the Special Issue Recent Developments in the Prion Field)
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. View Full-Text
Keywords: Prion; Protein misfolding cyclic amplification; molecular model; interspecies barrier Prion; Protein misfolding cyclic amplification; molecular model; interspecies barrier
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Levavasseur, E.; Privat, N.; Martin, J.-C.E.; Simoneau, S.; Baron, T.; Flan, B.; Torres, J.-M.; Haïk, S. Molecular Modeling of Prion Transmission to Humans. Viruses 2014, 6, 3766-3777.

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