Location: Virus and Prion ResearchTitle: Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer
|MOORE, S.JO - Oak Ridge Institute For Science And Education (ORISE)
|WEST GREENLEE, HEATHER - Iowa State University
Submitted to: PLoS Pathogens
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/9/2023
Publication Date: 12/4/2023
Citation: Kokemuller, R., Moore, S., Bian, J., West Greenlee, H.M., Greenlee, J.J. 2023. Disease phenotype of classical sheep scrapie is changed upon experimental passage through white-tailed deer. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1011815.
Interpretive Summary: Transmissible spongiform encephalopathies (TSEs) are a group of fatal diseases caused by the accumulation of misfolded prion protein in the brain. Ruminant species such as sheep, deer, and elk can get prion diseases. In sheep the disease is called scrapie. In deer and elk, the disease is called chronic wasting disease (CWD). The source of CWD is unknown, but one possibility is that scrapie jumped from sheep to deer. When we experimentally exposed white-tailed deer to the sheep scrapie agent, all deer developed scrapie. The purpose of the current experiment was to determine if sheep can get scrapie derived from white-tailed deer. Some sheep developed scrapie after oronasal exposure to the scrapie agent from white-tailed deer. Passage through white-tailed deer results in a scrapie isolate with different strain properties than the original inoculum. The detection of new strain properties was an unexpected result that will be the subject of further studies. These results indicate that sheep could be susceptible to the scrapie agent after passage through deer if exposed to the agent in natural or agricultural settings, which could be a confounding factor to the scrapie eradication program. National and state regulatory and wildlife officials should consider this information when developing plans to reduce or eliminate TSEs.
Technical Abstract: Transmissible spongiform encephalopathy (TSE) agents have strain variations that influence disease phenotype and may affect the potential for interspecies transmission. Since deer and sheep may use the same grazing land, it is important to understand the potential transmission of TSEs between these species. The US scrapie isolate (No.13-7) had a 100% attack rate in white-tailed deer after oronasal challenge. The purpose of this study was to determine if sheep are susceptible to oronasal challenge with the scrapie agent from white-tailed deer. Suffolk lambs of various prion protein genotypes were challenged by the oronasal route with a 10% brain homogenate from scrapie-affected white-tailed deer. Sheep were euthanized and necropsied upon development of clinical signs or at the end of the experiment (72 months post-inoculation). Tissues were tested for PrPSc by enzyme immunoassay, western blot, and immunohistochemistry. The first sheep (2/2) to develop clinical signs at approximately 29 months post-inoculation (MPI) had the VRQ/VRQ genotype. One of the two sheep with the ARQ/ARQ genotype also developed clinical signs at 48 MPI. This is in contrast to the original No.13-7 inoculum that has a faster incubation period in sheep with the ARQ/ARQ genotype compared to sheep of the VRQ/VRQ genotype. The shorter incubation period in VRQ/VRQ sheep than ARQ/ARQ sheep after passage through deer indicates a phenotype change. This is important because scrapie infected deer could transmit disease to sheep resulting in new scrapie strain properties. This work raises the concern that scrapie infected deer could serve as a confounding factor to scrapie eradication programs as the scrapie agent from deer is transmissible to sheep by the oronasal route.