The chronic wasting disease agent from white-tailed deer fails to adapt to sheep upon second passage

Authors: FRESE, ALEXIS - Oak Ridge Institute For Science And Education (ORISE); Cassmann, Eric; WEST GREENLEE, HEATHER - Iowa State University; Greenlee, Justin

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/22/2022
Publication Date: 9/13/2022
Citation: Frese, A.J., Cassmann, E.D., West Greenlee, H.M., Greenlee, J.J. 2022. The chronic wasting disease agent from white-tailed deer fails to adapt to sheep upon second passage. Prion 2022 Conference abstracts: pushing the boundaries. 16(1):144. https://doi.org/10.1080/19336896.2022.2091286.
DOI: https://doi.org/10.1080/19336896.2022.2091286

Interpretive Summary:

Technical Abstract: Interspecies transmission of prion disease is highly variable and dependent upon multiple factors. The chronic wasting disease (CWD agent) of mule deer 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 white-tailed deer and to characterize subsequent passages of the resulting disease agent. Suffolk sheep (n=15) with PRNP genotypes VRQ/ARQ, ARQ/ARQ, or ARQ/ARR were inoculated intracranially with CWD prions from white-tailed deer. Western blots and ELISA assays were performed on brain and lymphoid tissues to analyze PrPSc accumulation. Brain material from one positive sheep with the ARQ/ARQ genotype (#424) was used to inoculate mice expressing the mouse (C57BL/6; 20 ul of 10% homogenate) or sheep VRQ (Tg338; 20 ul of 1% homogenate) PRNP. PrPSc was detected in 4/15 sheep in the brainstem at the level of the obex, with an average incubation period of 41 months. Sheep #424 (the animal whose brain was passaged to mice) also had PrPSc in the cerebrum, but PrPSc was not detectable in any lymphoid tissues. Inoculum from the CWD-positive sheep did not cause disease or result in detectable PrPSc in ovinized mice (Tg338) after incubation of 800 days. However, upon passage to C57BL/6, 4/20 mice were positive with an average incubation period of 684 days. Upon second passage to C57BL/6 mice, the attack rate increased to 14/15 with a mean incubation period of 380 dpi. The CWD agent from white-tailed deer transmits to sheep via intracranial inoculation demonstrating that there is not an absolute species barrier between sheep and white-tailed deer. In affected sheep, distribution of PrPSc was limited to the central nervous system, suggesting that environmental shedding of CWD prions from sheep would be negligible. CWD isolates from cervids usually do not transmit to wild-type mice, but after passage through sheep, this isolate readily passed to C57BL/6 mice. It was unexpected that the CWD agent from sheep did not further adapt in Tg338 mice. This data suggests that the CWD agent from white-tailed deer is unlikely to present a major risk to sheep, but further assessments should be conducted in mice expressing the ARQ ovine prion protein.