Bovine adapted transmissible mink encephalopathy is similar to L-BSE after passage through sheep with the VRQ/VRQ genotype but not VRQ/ARQ

Eric Cassmann,Martin Groschup,Justin Greenlee,Eric Nicholson,Sarah Jo Moore,Robyn Kokemuller,Anne Balkema-Buschmann

doi:10.1186/s12917-020-02611-0

Abstract

BackgroundTransmissible 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 L-BSE 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.ResultsSheep 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.ConclusionsOur 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.

Highlights

Transmissible mink encephalopathy (TME) is a fatal neurologic disease of farmed mink
We previously reported that sheep are susceptible to bovine adapted TME after intracranial inoculation [13], and the resulting disease phenotype is similar to L-type bovine spongiform encephalopathy (BSE) (L-BSE) in sheep with Scrapie/ disease associated prion protein (PrPSc) not detected in lymphoid tissues [14, 15]
Transgenic mouse expressing wildtype bovine Cellular prion protein (PrPC) (TgBovXV) mice inoculated with o-bTMEVV, o-bTMEAV, bovine adapted TME (bTME), L-BSE, and Classical BSE (C-BSE) had attack rates of 95% (20/21), 79% (15/19), 90% (18/20), 100% (18/18), and 100% (18/18), respectively

Summary

Introduction

Transmissible mink encephalopathy (TME) is a fatal neurologic disease of farmed mink. There are numerous TSEs affecting different species including Creutzfeldt-Jakob disease (CJD) in humans [2], bovine spongiform encephalopathy (BSE) [3], scrapie in sheep [4], and transmissible mink encephalopathy (TME) [5]. We previously reported that sheep are susceptible to bovine adapted TME (bTME) after intracranial inoculation [13], and the resulting disease phenotype is similar to L-BSE in sheep with PrPSc not detected in lymphoid tissues [14, 15]. These similarities prompted an investigation to compare ovine passaged bovine TME (obTME) with other TSEs from cattle, C-BSE and L-BSE

Methods

Results

Discussion

Conclusion