The emergence of classical #BSE from atypical/Nor98 #scrapie (Proc Natl Acad Sci USA, abstract)

[Source: Proceedings of the National Academy of Sciences of the United States of America, full page: (LINK). Abstract, edited.]

The emergence of classical BSE from atypical/Nor98 scrapie

Alvina Huor, Juan Carlos Espinosa, Enric Vidal, Hervé Cassard, Jean-Yves Douet, Séverine Lugan, Naima Aron, Alba Marín-Moreno, Patricia Lorenzo, Patricia Aguilar-Calvo, Juan Badiola, Rosa Bolea, Martí Pumarola, Sylvie L. Benestad, Leonore Orge, Alana M. Thackray, Raymond Bujdoso, Juan-Maria Torres, and Olivier Andreoletti

PNAS first published December 16, 2019 / DOI:

Edited by Michael B. A. Oldstone, Scripps Research Institute, La Jolla, CA, and approved November 15, 2019 (received for review September 11, 2019)



The origin of transmissible BSE in cattle remains unestablished. Sheep scrapie is a potential source of this known zoonotic. Here we investigated the capacity of sheep scrapie to propagate in bovine PrP transgenic mice. Unexpectedly, transmission of atypical but not classical scrapie in bovine PrP mice resulted in propagation of classical BSE prions. Detection of prion seeding activity by in vitro protein misfolding cyclic amplification demonstrated BSE prions in the original atypical scrapie isolates. BSE prion seeding activity was also detected in ovine PrP mice inoculated with limiting dilutions of atypical scrapie. Our data demonstrate that classical BSE prions can emerge during intra- and interspecies passage of atypical scrapie and provide an unprecedented insight into the evolution of mammalian prions.



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.

prion – atypical scrapie – c-BSE



1 A.H., J.C.E., and E.V. contributed equally to the work.

2 To whom correspondence may be addressed. Email:

Author contributions: E.V. and O.A. designed research; A.H., J.C.E., E.V., H.C., J.-Y.D., S.L., N.A., A.M.-M., P.L., P.A.-C., J.B., R. Bolea, M.P., and O.A. performed research; S.L.B. and L.O. contributed new reagents/analytic tools; A.H., J.C.E., E.V., S.L.B., L.O., A.M.T., R. Bujdoso, J.M.T., and O.A. analyzed data; and A.H., S.L.B., L.O., A.M.T., R. Bujdoso, and O.A. wrote the paper.

The authors declare no competing interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at

Published under the PNAS license.

Keywords: Prions; BSE; Cattle; Scrapie.


#Ganglioside synthase knock-out reduces #prion disease #incubation time in mouse models (Am J Pathol., abstract)

[Source: American Journal of Pathology, full page: (LINK). Abstract, edited.]

Ganglioside synthase knock-out reduces prion disease incubation time in mouse models

Atsushi Kobayashi, , Zechen Qi, Taishi Shimazaki, Yoshiko Munesue, Tomomi Miyamoto, Norikazu Isoda, Hirofumi Sawa, Keisuke Aoshima, Takashi Kimura, Shirou Mohri, Tetsuyuki Kitamoto, Tadashi Yamashita, Ichiro Miyoshi


Accepted: November 16, 2018 – Received in revised form: November 14, 2018 – Received: September 4, 2018



Localization of the abnormal and normal isoforms of prion proteins to detergent-resistant membrane microdomains, lipid rafts, is important for the conformational conversion. Lipid rafts are enriched in sialic acid–containing glycosphingolipids, namely gangliosides. Alteration in the ganglioside composition of lipid rafts can affect the localization of lipid raft–associated proteins. To investigate the role of gangliosides in the pathogenesis of prion diseases, we performed intracerebral transmission study of a scrapie prion strain Chandler and a Gerstmann-Sträussler-Scheinker syndrome prion strain Fukuoka-1 using various knock-out mouse strains ablated with ganglioside synthase gene, ie, GD2/GM2 synthase, GD3 synthase, or GM3 synthase. Following challenge with the Chandler strain, GD2/GM2 synthase knock-out mice showed 20% reduction of incubation time, reduced prion protein deposition in the brain with attenuated glial reactions, and reduced localization of prion proteins to lipid rafts. These results raise the possibility that the gangliosides may have an important role in prion disease pathogenesis by affecting the localization of prion proteins to lipid rafts.

Funding: Supported by Grants-in-Aid for Scientific Research from JSPS (18K05963; A.K.), The Ichiro Kanehara Foundation (A.K.), The Suhara Memorial Foundation (A.K.), and The Kato Memorial Trust for Nambyo Research (A.K.).

Disclosures: None declared.

© 2018 Published by Elsevier Inc. on behalf of the American Society for Investigative Pathology.

Keywords: Prions; Scrapie; Gangliosides; Animal models.


The #EU #summary #report on #surveillance for the presence of transmissible spongiform #encephalopathies (#TSEs) in 2017 (EFSA, abstract)

[Source: European Food Safety Authority (EFSA), full page: (LINK). Abstract, edited.]

Scientific Report  / Open Access

The European Union summary report on surveillance for the presence of transmissible spongiform encephalopathies (TSEs) in 2017

European Food Safety Authority (EFSA) / First published: 28 November 2018 / DOI:


Requestor: European Commission

Question number: EFSA‐Q‐2017‐00753

Acknowledgements: EFSA wishes to thank for the support provided to this scientific output to the EFSA staff members: Yves Van der Stede, Angel Ortiz Pelaez, Valentina Rizzi, Pietro Stella and Frank Boelaert, and to the EFSA contractor: Istituto Zooprofilattico Sperimentale del Piemonte, Liguria e Valle d’Aosta (Unit BEAR – Biostatistica Epidemiologia e Analisi del Rischio and staff: Giuseppe Ru, Francesco Ingravalle, Cristina Bona, Rosanna Desiato, Cristiana Maurella and Eleonora Aiassa).

Approved: 6 November 2018



This report presents the results of surveillance on transmissible spongiform encephalopathies (TSEs) in bovine animals, sheep, goats, cervids and other animal species, as well as genotyping in sheep, carried out in 2017 in the European Union (EU) according to Regulation (EC) 999/2001, and in Iceland, Norway and Switzerland. In total, 1,312,714 cattle were tested by the 28 EU Member States (MSs) which is a decrease of 3% compared with 2016; 18,526 were tested by the three non‐MSs. For the first time since bovine spongiform encephalopathy (BSE) has been reported, no cases of classical BSE were reported in 2017. Six atypical BSE cases were reported by three different MSs: Spain 1 H‐BSE/2 L‐BSE; France 1 H‐BSE/1 L‐BSE; and Ireland 1 L‐BSE. Over the year, 314,547 sheep and 117,268 goats were tested in the EU. In sheep, 933 cases of scrapie were reported: 839 classical and unknown (145 index cases) by eight MSs and 94 atypical (89 index cases) by 13 MSs. Fourteen ovine scrapie cases were reported by Iceland and Norway. Of all classical scrapie cases, 98.2% occurred in sheep with genotypes of susceptible groups. The genotyping of a random sample in 21 MSs showed that 26.5% of the genotyped sheep carried genotypes of the susceptible groups. In goats 567 cases of scrapie were reported: 558 classical (42 index cases) by seven MSs and nine atypical (seven index cases) by five MSs. In total, 3,585 cervids were tested for TSE by ten MSs, mostly by Romania. All results were negative. Eleven cases of chronic wasting disease (CWD) cases were reported in cervids by Norway: nine wild reindeer, one moose and, for the first time ever, one red deer. In total, 185 animals from five species other than cattle, small ruminants and cervids were tested by three MSs, with negative results.

Keywords: Prions; TSE; Mad Cow; Scrapie; Chronic Wasting Disease; Cattle; Cervids; Sheeps; EU.