Second passage of chronic wasting disease of mule deer in sheep compared to classical scrapie after intracranial inoculation

Authors: Cassmann, Eric; FRESE, RYLIE - Orise Fellow; Greenlee, Justin

Submitted to: Journal of Veterinary Diagnostic Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/25/2020
Publication Date: 5/28/2021
Citation: Cassmann, E.D., Frese, R., Greenlee, J.J. 2021. Second passage of chronic wasting disease of mule deer in sheep compared to classical scrapie after intracranial inoculation. Journal of Veterinary Diagnostic Investigation. 33(4):711-720. https://doi.org/10.1177/10406387211017615.
DOI: https://doi.org/10.1177/10406387211017615

Interpretive Summary: Chronic wasting disease (CWD) is a fatal and uncurable brain disease of deer and elk that is related to a similar disease in sheep called scrapie. Both diseases are cause by a misfolded protein called a prion. The exact origin of CWD is unknown, but a possible origin could have been spread of sheep scrapie to deer. Previous research found indistinguishable traits in common between CWD in deer and scrapie in sheep. Additionally, it is unknown if deer CWD can naturally transmit to sheep. In this research, we show that abnormal prions spread throughout the body of sheep intracranially infected with CWD similar to how scrapie spreads in sheep. We compared two US classical scrapie strains to CWD in sheep and found that one of these strains is indistinguishable from sheep CWD. These results demonstrate that current diagnostic techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred in a natural setting. This research reinforces the need to continue ongoing cross-species transmission studies focusing on oral susceptibility of sheep to CWD and develop techniques to discriminate sheep CWD from sheep scrapie.

Technical Abstract: The origin of chronic wasting disease (CWD) in cervids is unclear. One hypothesis suggests that CWD originated from scrapie in sheep. In this experiment, we had two main objectives. The first objective was to determine if CWD adaptation in sheep alters the disease phenotype. The second objective was to determine if the disease phenotype of sheep adapted CWD is distinct from classical scrapie. We intracranially inoculated sheep with brain homogenate from first passage mule deer CWD in sheep (sCWDmd). The attack rate in second passage sheep was 100% (12/12). Sheep had prominent lymphoid accumulations of PrPSc reminiscent of classical scrapie. The pattern and distribution of PrPSc in the brains of sheep with CWDmd was similar to scrapie strain 13-7 but different from scrapie strain x124. The western blot glycoprofiles of sCWDmd were indistinguishable from scrapie strain 13-7; however, independent of sheep genotype, glycoprofiles of sCWDmd were different than x124. When sheep genotypes were evaluated individually, there was considerable overlap in the glycoprofiles that precluded significant discrimination between sheep CWD and scrapie strains. Taken together, these data suggest that the phenotype of CWD in sheep is indistinguishable from some strains of scrapie in sheep. Given the results of this study, current diagnostic techniques would be unlikely to distinguish CWD in sheep from scrapie in sheep if cross-species transmission occurred naturally. It is unknown if sheep are naturally vulnerable to CWD; however, the susceptibility of sheep after intracranial inoculation and lymphoid accumulation indicates that the species barrier is not absolute.