title: Bovine spongiform encephalopathy induces misfolding of alleged prion-resistant species cellular prion protein without altering its pathobiological features.
abstract: Bovine spongiform encephalopathy (BSE) prions were responsible for an unforeseen epizootic in cattle which had a vast social, economic, and public health impact. This was primarily because BSE prions were found to be transmissible to humans. Other species were also susceptible to BSE either by natural infection (e.g., felids, caprids) or in experimental settings (e.g., sheep, mice). However, certain species closely related to humans, such as canids and leporids, were apparently resistant to BSE. In vitro prion amplification techniques (saPMCA) were used to successfully misfold the cellular prion protein (PrP(c)) of these allegedly resistant species into a BSE-type prion protein. The biochemical and biological properties of the new prions generated in vitro after seeding rabbit and dog brain homogenates with classical BSE were studied. Pathobiological features of the resultant prion strains were determined after their inoculation into transgenic mice expressing bovine and human PrP(C). Strain characteristics of the in vitro-adapted rabbit and dog BSE agent remained invariable with respect to the original cattle BSE prion, suggesting that the naturally low susceptibility of rabbits and dogs to prion infections should not alter their zoonotic potential if these animals became infected with BSE. This study provides a sound basis for risk assessment regarding prion diseases in purportedly resistant species.
authors: CIC bioGUNE, 48160 Derio, Bizkaia, Spain, IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Bizkaia, Spain.
authors: Enric
authors: E
authors: Vidal
authors: Natalia
authors: N
authors: Fernández-Borges
authors: Belén
authors: B
authors: Pintado
authors: Montserrat
authors: M
authors: Ordóñez
authors: Mercedes
authors: M
authors: Márquez
authors: Dolors
authors: D
authors: Fondevila
authors: Juan María
authors: JM
authors: Torres
authors: Martí
authors: M
authors: Pumarola
authors: Joaquín
authors: J
authors: Castilla
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002417:Cattle; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004285:Dogs; D016643:Encephalopathy, Bovine Spongiform / Q000378:metabolism* / Q000401:mortality / Q000635:transmission*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D021141:Nucleic Acid Amplification Techniques / Q000379:methods; D011328:Prions / Q000378:metabolism*; D057165:Proteostasis Deficiencies / Q000209:etiology* / Q000401:mortality / Q000473:pathology; D011817:Rabbits; D013045:Species Specificity; D016019:Survival Analysis
chemical_list: D011328:Prions
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