title: Elements modulating the prion species barrier and its passage consequences.
abstract: 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.
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Juan-Maria
authors.initials: JM
authors.lastname: Torres
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Juan-Carlos
authors.initials: JC
authors.lastname: Espinosa
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Aguilar-Calvo
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: María-Eugenia
authors.initials: ME
authors.lastname: Herva
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Aroa
authors.initials: A
authors.lastname: Relaño-Ginés
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Villa-Diaz
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Morales
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Parra
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Elia
authors.initials: E
authors.lastname: Alamillo
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Brun
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain; CIC bioGUNE and IKERBASQUE, Basque Foundation for Science, Derio-Bilbao, Bizkaia, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Castilla
authors.affiliation: Centro de Investigación en Sanidad Animal (CISA-INIA), Valdeolmos, Madrid, Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Molina
authors.affiliation: Animal Health and Veterinary Laboratories Agency (AHVLA) New Haw, Addlestone, Surrey, United Kingdom.
authors.forename: Steve A C
authors.initials: SA
authors.lastname: Hawkins
authors.affiliation: UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, École Nationale Vétérinaire de Toulouse, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Andreoletti
mesh_terms: D000818:Animals; D002417:Cattle; D004195:Disease Models, Animal; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism*; D012756:Sheep; D013552:Swine
chemical_list: D011328:Prions