1. Porcine Prion Protein as a Paradigm of Limited Susceptibility to Prion Strain Propagation
- Author
-
Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), European Commission, Food Standards Agency (UK), Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba (0000-0002-4023-6398), Benestad, Sylvie L (0000-0002-3011-0484), Andreoletti, Olivier (0000-0002-7369-6016), Torres, Juan María (0000-0003-0443-9232), Espinosa Martín, Juan Carlos, Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Benestad, Sylvie L., Andréoletti, Olivier, Torres, Juan María, Ministerio de Economía y Competitividad (España), Agencia Estatal de Investigación (España), European Commission, Food Standards Agency (UK), Espinosa Martín, Juan Carlos [0000-0002-6719-9902], Marín-Moreno, Alba (0000-0002-4023-6398), Benestad, Sylvie L (0000-0002-3011-0484), Andreoletti, Olivier (0000-0002-7369-6016), Torres, Juan María (0000-0003-0443-9232), Espinosa Martín, Juan Carlos, Marín-Moreno, Alba, Aguilar-Calvo, Patricia, Benestad, Sylvie L., Andréoletti, Olivier, and Torres, Juan María
- Abstract
Although experimental transmission of bovine spongiform encephalopathy (BSE) to pigs and transgenic mice expressing pig cellular prion protein (PrPC) (porcine PrP [PoPrP]-Tg001) has been described, no natural cases of prion diseases in pig were reported. This study analyzed pig-PrPC susceptibility to different prion strains using PoPrP-Tg001 mice either as animal bioassay or as substrate for protein misfolding cyclic amplification (PMCA). A panel of isolates representatives of different prion strains was selected, including classic and atypical/Nor98 scrapie, atypical-BSE, rodent scrapie, human Creutzfeldt-Jakob-disease and classic BSE from different species. Bioassay proved that PoPrP-Tg001-mice were susceptible only to the classic BSE agent, and PMCA results indicate that only classic BSE can convert pig-PrPC into scrapie-type PrP (PrPSc), independently of the species origin. Therefore, conformational flexibility constraints associated with pig-PrP would limit the number of permissible PrPSc conformations compatible with pig-PrPC, thus suggesting that pig-PrPC may constitute a paradigm of low conformational flexibility that could confer high resistance to the diversity of prion strains.
- Published
- 2021