The chronic wasting disease agent from white-tailed deer is highly infectious to humanized mice after passage through raccoons

Authors: Cassmann, Eric; QI, XU - Case Western Reserve University (CWRU); KONG, QINGZHONG - Case Western Reserve University (CWRU); Greenlee, Justin

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/22/2022
Publication Date: 9/13/2022
Citation: Cassmann, E.D., Qi, X., Kong, Q., Greenlee, J.J. 2022. The chronic wasting disease agent from white-tailed deer is highly infectious to humanized mice after passage through raccoons. Prion 2022 Conference abstracts: pushing the boundaries. 16(1):120. https://doi.org/10.1080/19336896.2022.2091286.
DOI: https://doi.org/10.1080/19336896.2022.2091286

Interpretive Summary:

Technical Abstract: The purpose of this work was to evaluate the zoonotic potential of the raccoon passaged chronic wasting disease (CWD) agent in humanized transgenic mice in comparison with the North American CWD agent from the original white-tailed deer host. Pooled brain material (GG96) from a CWD positive herd was used to oronasally inoculate two white-tailed deer with wild-type prion protein genotype and intracranially inoculate a raccoon. Brain homogenates (10% w/v) from the raccoon and the two white-tailed deer were used to intracranially inoculate separate groups of transgenic mice that express human prion protein with methionine (M) at codon 129 (Tg40h). Brains and spleens were collected from mice at experimental endpoints of clinical disease or approximately 700 days post-inoculation. Tissues were divided and homogenized or fixed in 10% buffered neutral formalin. Immunohistochemistry, enzyme immunoassay, and western blot were used to detect misfolded prion protein (PrPSc) in tissue. Humanized transgenic mice inoculated with the raccoon passaged CWD agent from white-tailed deer exhibited a 100% (12/12) attack rate with an average incubation period of 605 days. PrPSc was detected in brain tissue by enzyme immunoassay with an average optical density of 3.6/4.0 for positive brains. PrPSc also was detected in brain tissue by western blot and immunohistochemistry. No PrPSc was detected in the spleens of mice inoculated with the raccoon passaged CWD agent. Humanized mice inoculated with the CWD agent from white-tailed deer did not have detectable PrPSc using conventional immunoassay techniques. The host range of the CWD agent from white-tailed deer was expanded in our experimental model after one passage through raccoons.