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BSE can propagate in sheep co-infected or pre-infected with scrapie

Chong, Angela; Foster, James D; Goldmann, Wilfred; Gonzalez, Lorenzo; Jeffrey, Martin; O'Connor, Matthew J; Bishop, Keith; Maddison, Ben C; Houston, E. Fiona; Gough, Kevin C.; Hunter, Nora


Angela Chong

James D Foster

Wilfred Goldmann

Lorenzo Gonzalez

Martin Jeffrey

Matthew J O'Connor

Keith Bishop

Ben C Maddison

E. Fiona Houston

Professor of Biochemistry and Pathology

Nora Hunter


To understand the possible role of mixed-prion infections in disease presentation, the current study reports the co-infection of sheep with bovine spongiform encephalopathy (BSE) and scrapie. The bovine BSE agent was inoculated subcutaneously into sheep with ARQ/ARQ or VRQ/ARQ PRNP genotypes either at the same time as subcutaneous challenge with scrapie, or three months later. In addition, VRQ/VRQ sheep naturally infected with scrapie after being born into a scrapie-affected flock were challenged subcutaneously with BSE at eight or twenty one months-of-age. Sheep were analysed by incubation period/attack rate, and western blot of brain tissue determined the presence of BSE or scrapie-like PrP Sc. Serial protein misfolding cyclic amplification (sPMCA) that can detect very low levels of BSE in the presence of an excess of scrapie agent was also applied to brain and lymphoreticular tissue. For VRQ/ARQ sheep challenged with mixed infections, scrapie-like incubation periods were produced, and no BSE agent was detected. However, whilst ARQ/ARQ sheep developed disease with BSE-like incubation periods, some animals had a dominant scrapie western blot phenotype in brain, but BSE was detected in these sheep by sPMCA. In addition, VRQ/VRQ animals challenged with BSE after natural exposure to scrapie had scrapie-like incubation periods and dominant scrapie PrP Sc in brain, but one sheep had BSE detectable by sPMCA in the brain. Overall, the study demonstrates for the first time that for scrapie/BSE mixed infections, VRQ/ARQ sheep with experimental scrapie did not propagate BSE but VRQ/VRQ sheep with natural scrapie could propagate low levels of BSE, and whilst BSE readily propagated in ARQ/ARQ sheep it was not always the dominant PrP Sc strain in brain tissue. Indeed, for several animals, a dominant scrapie biochemical phenotype in brain did not preclude the presence of BSE prion.


Chong, A., Foster, J. D., Goldmann, W., Gonzalez, L., Jeffrey, M., O'Connor, M. J., …Hunter, N. (2021). BSE can propagate in sheep co-infected or pre-infected with scrapie. Scientific Reports, 11, Article 11931.

Journal Article Type Article
Acceptance Date May 24, 2021
Online Publication Date Jun 7, 2021
Publication Date Jun 7, 2021
Deposit Date May 26, 2021
Publicly Available Date Jun 7, 2021
Journal Scientific Reports
Print ISSN 2045-2322
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 11
Article Number 11931
Keywords Multidisciplinary
Public URL
Publisher URL


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