000087581 001__ 87581 000087581 005__ 20210310171108.0 000087581 0247_ $$2doi$$a10.1073/pnas.1915737116 000087581 0248_ $$2sideral$$a115782 000087581 037__ $$aART-2019-115782 000087581 041__ $$aeng 000087581 100__ $$aHuor, A. 000087581 245__ $$aThe emergence of classical BSE from atypical/Nor98 scrapie 000087581 260__ $$c2019 000087581 5060_ $$aAccess copy available to the general public$$fUnrestricted 000087581 5203_ $$aAtypical/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. 000087581 536__ $$9info:eu-repo/grantAgreement/ES/MINECO/AGL2016-78054-R$$9info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA 282-13-TRANSPRION$$9info:eu-repo/grantAgreement/EUR/INTERREG-POCTEFA/EFA-148-16 REDPRION$$9info:eu-repo/grantAgreement/EC/FP7/222887/EU/Protecting the food chain from prions: shaping European priorities through basic and applied research/PRIORITY 000087581 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/ 000087581 590__ $$a9.412$$b2019 000087581 591__ $$aMULTIDISCIPLINARY SCIENCES$$b8 / 71 = 0.113$$c2019$$dQ1$$eT1 000087581 592__ $$a5.165$$b2019 000087581 593__ $$aMultidisciplinary$$c2019$$dQ1 000087581 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000087581 700__ $$aEspinosa, J.C. 000087581 700__ $$aVidal, E. 000087581 700__ $$aCassard, H. 000087581 700__ $$aDouet, J.Y. 000087581 700__ $$aLugan, S. 000087581 700__ $$aAron, N. 000087581 700__ $$aMarµn-Moreno, A. 000087581 700__ $$aLorenzo, P. 000087581 700__ $$aAguilar-Calvo, P. 000087581 700__ $$0(orcid)0000-0002-7173-7216$$aBadiola, J.$$uUniversidad de Zaragoza 000087581 700__ $$0(orcid)0000-0002-2746-3932$$aBolea, R.$$uUniversidad de Zaragoza 000087581 700__ $$aPumarola, M. 000087581 700__ $$aBenestad, S.L. 000087581 700__ $$aOrge, L. 000087581 700__ $$aThackray, A.M. 000087581 700__ $$aBujdoso, R. 000087581 700__ $$aTorres, J.M. 000087581 700__ $$aAndreoletti, O. 000087581 7102_ $$11009$$2773$$aUniversidad de Zaragoza$$bDpto. Patología Animal$$cÁrea Sanidad Animal 000087581 773__ $$g116, 52 (2019), 26853-26862$$pProc. Natl. Acad. Sci.$$tProceedings of the National Academy of Sciences$$x0027-8424 000087581 8564_ $$s1537384$$uhttps://zaguan.unizar.es/record/87581/files/texto_completo.pdf$$yVersión publicada 000087581 8564_ $$s144954$$uhttps://zaguan.unizar.es/record/87581/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000087581 909CO $$ooai:zaguan.unizar.es:87581$$particulos$$pdriver 000087581 951__ $$a2021-03-10-17:01:23 000087581 980__ $$aARTICLE