Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genoty
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RESEARCH ARTICLE
Open Access
Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ Eric Cassmann1,2, Sarah Jo Moore1,2, Robyn Kokemuller1, Anne Balkema-Buschmann3, Martin Groschup3, Eric Nicholson1 and Justin Greenlee1*
Abstract Background: Transmissible mink encephalopathy (TME) is a fatal neurologic disease of farmed mink. Evidence indicates that TME and L-BSE are similar and may be linked in some outbreaks of TME. We previously transmitted bovine adapted TME (bTME) to sheep. The present study compared ovine passaged bTME (o-bTME) to C-BSE and LBSE in transgenic mice expressing wild type bovine prion protein (TgBovXV). To directly compare the transmission efficiency of all prion strains in this study, we considered the attack rates and mean incubation periods. Additional methods for strain comparison were utilized including lesion profiles, fibril stability, and western blotting. Results: Sheep donor genotype elicited variable disease phenotypes in bovinized mice. Inoculum derived from a sheep with the VRQ/VRQ genotype (o-bTMEVV) resulted in an attack rate, incubation period, western blot profile, and neuropathology most similar to bTME and L-BSE. Conversely, donor material from a sheep with the VRQ/ARQ genotype (o-bTMEAV) elicited a phenotype distinct from o-bTMEVV, bTME and L-BSE. The TSE with the highest transmission efficiency in bovinized mice was L-BSE. The tendency to efficiently transmit to TgBovXV mice decreased in the order bTME, C-BSE, o-bTMEVV, and o-bTMEAV. The transmission efficiency of L-BSE was approximately 1.3 times higher than o-bTMEVV and 3.2 times higher than o-bTMEAV. Conclusions: Our findings provide insight on how sheep host genotype modulates strain genesis and influences interspecies transmission characteristics. Given that the transmission efficiencies of L-BSE and bTME are higher than C-BSE, coupled with previous reports of L-BSE transmission to mice expressing the human prion protein, continued monitoring for atypical BSE is advisable in order to prevent occurrences of interspecies transmission that may affect humans or other species. Keywords: TME, Transmissible mink encephalopathy, L-BSE, Prion diseases, Prion, PRNP, PrPSc, Sheep, TSE, Transmissible spongiform encephalopathies, C-BSE
* Correspondence: [email protected] 1 Virus and Prion Research Unit, National Animal Disease Center, Agricultural Research Service, United States Department of Agriculture, 1920 Dayton Avenue, P.O. Box 70, Ames, IA 50010, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party mat
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