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From: TSS ()
Subject: Sheep-Passaged Bovine Spongiform Encephalopathy Agent Exhibits Altered Pathobiological Properties in Bovine-PrP Transgenic Mice
Date: December 28, 2006 at 8:41 am PST

Journal of Virology, January 2007, p. 835-843, Vol. 81, No. 2
0022-538X/07/$08.00+0 doi:10.1128/JVI.01356-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Sheep-Passaged Bovine Spongiform Encephalopathy Agent Exhibits Altered Pathobiological Properties in Bovine-PrP Transgenic Mice
Juan Carlos Espinosa,1 Olivier Andréoletti,2 Joaquín Castilla,1 María Eugenia Herva,1 Mónica Morales,1 Elia Alamillo,1 Fayna Díaz San-Segundo,1 Caroline Lacroux,2 Séverine Lugan,2 Francisco Javier Salguero,1 Jan Langeveld,3 and Juan María Torres1*
Centro de Investigación en Sanidad Animal, INIA, 28130 Valdeolmos, Madrid, Spain,1 UMR INRA-ENVT 1225, Interactions Hôte Agent Pathogène, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France,2 CIDC-Lelystad, 8203 AA Lelystad, The Netherlands3

Received 27 June 2006/ Accepted 22 October 2006

Sheep can be experimentally infected with bovine spongiform encephalopathy (BSE), and the ensuing disease is similar to scrapie in terms of pathogenesis and clinical signs. BSE infection in sheep is an animal and human health concern. In this study, the transmission in BoPrP-Tg110 mice of prions from BSE-infected sheep was examined and compared to the transmission of original cattle BSE in cattle and sheep scrapie prions. Our results indicate no transmission barrier for sheep BSE prions to infect BoPrP-Tg110 mice, but the course of the disease is accelerated compared to the effects of the original BSE isolate. The shortened incubation period of sheep BSE in the model was conserved in subsequent passage in BoPrP-Tg110 mice, indicating that it is not related to infectious titer differences. Biochemical signature, lesion profile, and PrPSc deposition pattern of both cattle and sheep BSE were similar. In contrast, all three sheep scrapie isolates tested showed an evident transmission barrier and further adaptation in subsequent passage. Taken together, those data indicate that BSE agent can be altered by crossing a species barrier, raising concerns about the virulence of this new prion towards other species, including humans. The BoPrP-Tg110 mouse bioassay should be considered as a valuable tool for discriminating scrapie and BSE in sheep.

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* Corresponding author. Mailing address: Centro de Investigación en Sanidad Animal, INIA, 28130 Valdeolmos, Madrid, Spain. Phone: 34 91 620 23 00. Fax: 34 91 620 22 47. E-mail: jmtorres@inia.es .

Published ahead of print on 1 November 2006.

http://jvi.asm.org/cgi/content/abstract/81/2/835?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=prion&searchid=1&FIRSTINDEX=0&volume=81&issue=2&resourcetype=HWCIT

TSS




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