Journal Article

Elements modulating the prion species barrier and its passage consequences

Alamillo, Elia, Spanish Ministerio de Ciencia e Innovacion [RTA2012-00004, AGL2005-03066]; European Union [CT-2001-01309, CT-2004-023183, CT2004-506579, CT2009-222887], Ikerbasque - Basque Foundation for Science, Villa-Diaz, Ana, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria = National Institute for Agricultural and Food Research and Technology (INIA), Aguilar-Calvo, Patricia, Animal Health and Veterinary Laboratories Agency (AHVLA), Interactions hôtes-agents pathogènes [Toulouse] (IHAP) ; Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT), Molina, Susana, Morales, Monica, Brun, Alejandro, Relaño-Ginès, Aroa, Castilla, Joaquin, Parra, Beatriz, Espinosa, Juan-Carlos, Hawkins, Steve A. C, Torres, Juan-María, Herva, Mar

2014

Overview

The specific characteristics of Transmissible Spongiform Encephalopathy (TSE) strains may be altered during passage across a species barrier. In this study we investigated the biochemical and biological characteristics of Bovine Spongiform Encephalopathy (BSE) after transmission in both natural host species (cattle, sheep, pigs and mice) and in transgenic mice overexpressing the corresponding cellular prion protein (PrPC) in comparison with other non-BSE related prions from the same species. After these passages, most features of the BSE agent remained unchanged. BSE-derived agents only showed slight modifications in the biochemical properties of the accumulated PrPSc, which were demonstrated to be reversible upon re-inoculation into transgenic mice expressing bovine-PrPC. Transmission experiments in transgenic mice expressing bovine, porcine or human-PrP revealed that all BSE-derived agents were transmitted with no or a weak transmission barrier. In contrast, a high species barrier was observed for the non-BSE related prions that harboured an identical PrP amino acid sequence, supporting the theory that the prion transmission barrier is modulated by strain properties (presumably conformation-dependent) rather than by PrP amino acid sequence differences between host and donor. As identical results were observed with prions propagated either in natural hosts or in transgenic mouse models, we postulate that the species barrier and its passage consequences are uniquely governed by the host PrPC sequence and not influenced by other host genetic factors. The results presented herein reinforce the idea that the BSE agent is highly promiscuous, infecting other species, maintaining its properties in the new species, and even increasing its capabilities to jump to other species including humans. These data are essential for the development of an accurate risk assessment for BSE.

• Publisher: CCSD,Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Amino acid sequence / Amino acids / Analysis / Animal experimentation / Animal genetic engineering / Animal models / Animals / Biology / Bovine spongiform encephalopathy / Brain research / BSE / Cattle / Creutzfeldt-Jakob disease / Disease Models, Animal / Disease transmission / Encephalopathy / Encephalopathy, Bovine Spongiform - metabolism / Experiments / Genetic factors / Infections / Inoculation / Laboratories / Life Sciences / Medicine / Mice / Mice, Transgenic / New species / Ovis aries / Prion Diseases - metabolism / Prion protein / Prions / Prions (Proteins) / Prions - metabolism / Properties (attributes) / Proteins / Risk assessment / Rodents / Sheep / Suidae / Swine / Transgenic animals / Transgenic mice / Transmissible spongiform encephalopathy / Veterinary Science
• ISBN: 0003324858000