Radical Change in Zoonotic Abilities of Atypical BSE Prion Strains as Evidenced by Crossing of Sheep Species Barrier in Transgenic Mice
Alba Marín‐Moreno, Alvina Huor, Juan Carlos Espinosa, Jean‐Yves Douet, Patricia Aguilar‐Calvo, Naïma Aron, Juan Píquer, Séverine Lugan, Patricia Lorenzo, Cécile Tillier, Hervé Cassard, Olivier Andréoletti, Juan María Torres
Abstract
P rion diseases, or transmissible spongiform en- cephalopathies (TSEs), are a group of rare and lethal neurodegenerative diseases that affect a great number of mammal species, including humans and animals belonging to the human food chain. The conversion of a host encoded cellular protein of unknown function (PrP C ) into a disease-associated isoform (PrP Sc ) is the molecular event underlying the development of TSEs. Such conformational change is driven by PrP Sc itself because it recruits and transforms PrP C molecules, acting as a template (1). The conformational change, associated with an increase of -sheet content, also results in a change in the protein biochemical features (2). Although PrP C is monomeric, protease-sensitive, and soluble in nonionic detergents, PrP Sc has a high tendency to aggregate, is partially resistant to protease digestion, and is insoluble in nonionic detergents (1,3).