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Título: | Mixtures of prion substrains in natural scrapie cases revealed by ovinised murine models |
Autor: | Barrio, Tomás; Filali, Hicham; Otero, Alicia; Sheleby-Elías, Jessica; Marín, Belén; Vidal, Enric; Béringue, V.; Torres, Juan María; Groschup, M. H.; Andréoletti, Olivier; Badiola, Juan J.; Bolea, Rosa | Fecha de publicación: | 19-mar-2020 | Editor: | Nature Publishing Group | Citación: | Scientific Reports 10(1): e5042 (2020) | Resumen: | Phenotypic variability in prion diseases, such as scrapie, is associated to the existence of prion strains, which are different pathogenic prion protein (PrPSc) conformations with distinct pathobiological properties. To faithfully study scrapie strain variability in natural sheep isolates, transgenic mice expressing sheep cellular prion protein (PrPC) are used. In this study, we used two of such models to bioassay 20 scrapie isolates from the Spain-France-Andorra transboundary territory. Animals were intracerebrally inoculated and survival periods, proteinase K-resistant PrP (PrPres) banding patterns, lesion profiles and PrPSc distribution were studied. Inocula showed a remarkable homogeneity on banding patterns, all of them but one showing 19-kDa PrPres. However, a number of isolates caused accumulation of 21-kDa PrPres in TgShp XI. A different subgroup of isolates caused long survival periods and presence of 21-kDa PrPres in Tg338 mice. It seemed that one major 19-kDa prion isoform and two distinct 21-kDa variants coexisted in source inocula, and that they could be separated by bioassay in each transgenic model. The reason why each model favours a specific component of the mixture is unknown, although PrPC expression level may play a role. Our results indicate that coinfection with more than one substrain is more frequent than infection with a single component. | Descripción: | 15 Pág. | Versión del editor: | https://doi.org/10.1038/s41598-020-61977-1 | URI: | http://hdl.handle.net/10261/337478 | DOI: | 10.1038/s41598-020-61977-1 | E-ISSN: | 2045-2322 |
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