title: Molecular modeling of prion transmission to humans.
abstract: 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.
authors.affiliation: 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. etienne.levavasseur@inserm.fr.
authors.forename: Etienne
authors.initials: E
authors.lastname: Levavasseur
authors.affiliation: 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. nicolas.privat@inserm.fr.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Privat
authors.affiliation: Centro de Investigacion en Sanidad Animal, Carretera de Algete a El Casar, 28130 Madrid, Spain. espinosa.juan@inia.es.
authors.forename: Juan-Carlos Espinosa
authors.initials: JC
authors.lastname: Martin
authors.affiliation: LFB Biomédicaments, 91958 Les Ulis, France. simoneaus@lfb.fr.
authors.forename: Steve
authors.initials: S
authors.lastname: Simoneau
authors.affiliation: Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité Maladies neurodégénératives, 69394 Lyon, France. thierry.baron@anses.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Baron
authors.affiliation: LFB Biomédicaments, 91958 Les Ulis, France. flan@lfb.fr.
authors.forename: Benoit
authors.initials: B
authors.lastname: Flan
authors.affiliation: Centro de Investigacion en Sanidad Animal, Carretera de Algete a El Casar, 28130 Madrid, Spain. jmtorres@inia.es.
authors.forename: Juan-Maria
authors.initials: JM
authors.lastname: Torres
authors.affiliation: 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. stephane.haik@courriel.upmc.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Haïk
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000635:transmission*; D016643:Encephalopathy, Bovine Spongiform / Q000635:transmission*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D011328:Prions / Q000502:physiology*; D017510:Protein Folding; D015203:Reproducibility of Results; D013045:Species Specificity
chemical_list: D011328:Prions