10.17863/CAM.46303
Huor, Alvina
Espinosa, Juan Carlos
0000-0002-6719-9902
Vidal, Enric
0000-0002-4965-3286
Cassard, Hervé
Douet, Jean-Yves
0000-0002-0426-4957
Lugan, Séverine
Aron, Naima
Marín-Moreno, Alba
0000-0002-4023-6398
Lorenzo, Patricia
Aguilar-Calvo, Patricia
Badiola, Juan
Bolea, Rosa
Pumarola, Martí
Benestad, Sylvie L
Orge, Leonore
Thackray, Alana M
Bujdoso, Raymond
Torres, Juan-Maria
0000-0003-0443-9232
Andreoletti, Olivier
0000-0002-7369-6016
The emergence of classical BSE from atypical/Nor98 scrapie.
Proceedings of the National Academy of Sciences
2019
atypical scrapie
c-BSE
prion
Apollo - University of Cambridge Repository
University of Cambridge
013meh722
2019-11-26
2019-11-26
2019-12-26
eng
Article
https://www.repository.cam.ac.uk/handle/1810/299238
10.1073/pnas.1915737116
All rights reserved
open.access
Atypical/Nor98 scrapie (AS) is a prion disease of small ruminants. Currently there are no efficient measures to control this form of prion disease, and, importantly, the zoonotic potential and the risk that AS might represent for other farmed animal species remains largely unknown. In this study, we investigated the capacity of AS to propagate in bovine PrP transgenic mice. Unexpectedly, the transmission of AS isolates originating from 5 different European countries to bovine PrP mice resulted in the propagation of the classical BSE (c-BSE) agent. Detection of prion seeding activity in vitro by protein misfolding cyclic amplification (PMCA) demonstrated that low levels of the c-BSE agent were present in the original AS isolates. C-BSE prion seeding activity was also detected in brain tissue of ovine PrP mice inoculated with limiting dilutions (endpoint titration) of ovine AS isolates. These results are consistent with the emergence and replication of c-BSE prions during the in vivo propagation of AS isolates in the natural host. These data also indicate that c-BSE prions, a known zonotic agent in humans, can emerge as a dominant prion strain during passage of AS between different species. These findings provide an unprecedented insight into the evolution of mammalian prion strain properties triggered by intra- and interspecies passage. From a public health perspective, the presence of c-BSE in AS isolates suggest that cattle exposure to small ruminant tissues and products could lead to new occurrences of c-BSE.
Alberta Innovates - Health Solutions (via University of Calgary)
PEX17006-201700013
National Centre for the Replacement Refinement and Reduction of Animals in Research
NC/R00093X/1