Differences between the white-tailed and mule deer chronic wasting disease agents after passage through sheep

Authors: FRESE, ALEXIS - Oak Ridge Institute For Science And Education (ORISE); CASSMANN, ERIC - Iowa State University; Bian, Jifeng; MANDELL, LEISA - Retired ARS Employee; SMADI, SURA - Oak Ridge Institute For Science And Education (ORISE); WEST GREENLEE, HEATHER - Iowa State University; Greenlee, Justin

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/2/2025
Publication Date: 7/22/2025
Citation: Frese, A.J., Cassmann, E.D., Bian, J., Mandell, L.Z., Smadi, S., West Greenlee, H.M., Greenlee, J.J. 2025. Differences between the white-tailed and mule deer chronic wasting disease agents after passage through sheep. Frontiers in Veterinary Science. 12. Article 1632936. https://doi.org/10.3389/fvets.2025.1632936.
DOI: https://doi.org/10.3389/fvets.2025.1632936

Interpretive Summary: Prion disease are fatal neurodegenerative diseases. Chronic wasting disease (CWD) is the prion disease primarily affecting cervids, while scrapie is the analogous disease in sheep. Both diseases involve prion accumulation in the central nervous and lymphoid tissues, leading to environmental shedding. CWD has been found in 36 U.S. states and various other countries, raising concerns about its transmission dynamics and interspecies risks. Additionally, there is a geographic overlap between where CWD has been detected and domestic sheep populations, begging whether sheep may be susceptible to the CWD agent. Previous studies demonstrated that the CWD agent from white-tailed deer (WTD) and mule deer (MD) transmits to sheep. Building upon this research, the current study investigates the transmission of the WTD and MD CWD agents into sheep and then further into transgenic mice expressing either the cervid or sheep prion protein. Results from this study suggest that the WTD CWD agent is unlikely to pose a significant risk to sheep, but it could potentially be transmissible back to the cervid population. In contrast, the MD CWD agent could possibly pose a greater risk to the cervid and sheep populations. This work will greatly benefit researchers and the sheep and cervid industries.

Technical Abstract: Chronic wasting disease (CWD) is a fatal prion disease that affects the cervid species, including white-tailed deer (WTD) (Odocoileus virginianus) and mule deer (MD) (Odocoileus hemionus). Interspecies transmission of CWD is highly variable and dependent upon multiple factors. CWD of MD is transmissible to sheep after intracranial inoculation, with similar clinical signs and incubation periods to scrapie. This study used sheep and transgenic mice to investigate the susceptibility of sheep to the CWD agent from WTD (WTD sheep CWD) when intracranially inoculated and to characterize the agent in subsequent passages. Suffolk sheep (n=15) with PRNP genotypes VRQ/ARQ, ARQ/ARQ, or ARQ/ARR were inoculated intracranially with the CWD agent from WTD. Western blots and enzyme immunoassays (EIA) were performed on brain and lymphoid tissues to analyze PrPSc accumulation. PrPSc was detected in 2/15 sheep in the brainstem at the level of the obex (both ARQ/ARQ sheep), with an average incubation period of 39 months. In affected sheep, distribution of PrPSc was limited to the central nervous system. Brain material from one positive sheep (ARQ/ARQ) was used to inoculate mice expressing the cervid (Tg12) and ovine (Tg338) prion protein gene. Passage of the WTD sheep CWD agent into cervidized mice resulted in an attack rate of 83% for PrPSc detection with an average incubation period of 377 days for all mice, while passage into ovinized mice resulted in no clinical signs or demonstration of PrPSc. These results were compared to the MD CWD agent from sheep (MD sheep CWD) being passed into cervidized and ovinized mice. There was an 86% attack rate in cervidized mice with an average incubation period of 646 days for all mice and an attack rate of 100% in ovinized mice with an average incubation period of 282 days. Overall, this data suggests that WTD CWD is unlikely to present a major risk to sheep but could be transmissible back to the cervid population. However, MD sheep CWD could present risk to both the cervid and sheep population. Future studies include further characterizing the WTD sheep CWD and MD sheep CWD agent when passaged back into the cervid and sheep population.