Raccoons accumulate PrPSc after intracranial inoculation with the agents of chronic wasting disease (CWD) or transmissible mink encephalopathy (TME) but not atypical scrapie

Authors: MOORE, S - Orise Fellow; Smith, Jodi; Richt, Juergen; Greenlee, Justin

Submitted to: Journal of Veterinary Diagnostic Investigation
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/22/2018
Publication Date: 1/29/2019
Citation: Moore, S.J., Smith, J.D., Richt, J., Greenlee, J.J. 2019. Raccoons accumulate PrPSc after intracranial inoculation with the agents of chronic wasting disease (CWD) or transmissible mink encephalopathy (TME) but not atypical scrapie. Journal of Veterinary Diagnostic Investigation. 31(2):200-209. https://doi.org/10.1177/1040638718825290.
DOI: https://doi.org/10.1177/1040638718825290

Interpretive Summary: The prion diseases are fatal diseases of animals and humans that cause damaging changes in the brain. Animal prion diseases include scrapie in sheep, chronic wasting disease (CWD) in cervids, and transmissible mink encephalopathy (TME) in ranch-raised mink. The infectious agent is an abnormal protein called a prion that has misfolded from its normal state. This study tested whether raccoons develop clinical disease and/or accumulate abnormal prion protein after inoculation with prion agents from different species: TME from cattle, raccoons, or hamsters that occurs in two forms with distinct clinical signs and molecular properties called hyper and drowsy; CWD from white-tailed deer or elk; and atypical (Nor-98) scrapie from sheep. All raccoons inoculated with TME from raccoons or cattle developed clinical disease with short survival times. Raccoons inoculated with CWD from white-tailed deer, CWD from elk, or 'hyper' TME from hamsters did not develop clinical disease, but abnormal prion protein was detected in the brains of 25% of the raccoons in each study. The amount of abnormal prion protein in the brains of these raccoons was much less than in the brains of raccoons inoculated with TME from raccoons or cattle. None of the raccoons inoculated with 'drowsy' TME from hamsters or atypical scrapie from sheep developed clinical disease or detectable abnormal prion protein. This work suggests that raccoons are susceptible to prion disease isolates from raccoons, cattle, white-tailed deer, and elk. Raccoons are omnivores that have a widespread geographical distribution and are known to scavenge animal carcasses. Therefore, they could provide a route of transmission of prions disease between farmed and wild animal species. This information is useful to farmers and people involved in control of prion disease in free-ranging animals.

Technical Abstract: The prion diseases are neurodegenerative diseases characterized by the accumulation of misfolded prion protein (PrP*Sc) in the brain and other tissues. Animal prion diseases include scrapie in sheep, chronic wasting disease (CWD) in cervids, and transmissible mink encephalopathy (TME) in ranch-raised mink. The objective of this study was to investigate the susceptibility of raccoons to various prion disease isolates, and to compare the clinicopathologic features of the resulting disease. Raccoon kits were inoculated intracranially with raccoon-passaged TME (TME*Rac), bovine-passaged TME (TME*Bov), hamster-adapted drowsy (TME*DY) or hyper TME (TME*HY), CWD from white-tailed deer (CWD*Wtd) or elk (CWD*Elk), or atypical (Nor-98) scrapie. Raccoons were euthanized when they developed clinical signs of prion disease or at study endpoint (<82 months post-inoculation). Brain was examined for the presence of spongiform change and disease-associated PrP*Sc was detected using an enzyme-linked immunoassay, western immunoblot, and immunohistochemistry. All raccoons inoculated with TME*Rac and TME*Bov developed clinical disease at around 6.6 months post-inoculation with widespread PrP*Sc accumulation in central nervous system tissues. PrP*Sc was detected in the brain from 1 out of 4 raccoons in each of the CWD*Wtd, CWD*Elk, and TME*HY inoculated groups. None of the raccoons inoculated with TME*DY or atypical scrapie developed clinical disease or detectable PrP*Sc accumulation. The results of this study indicate that raccoons are highly susceptible to infection with raccoon- and bovine-passaged TME, while CWD isolates from white-tailed deer or elk and hamster-adapted TME*HY transmit poorly. Raccoons appear to be resistant to infection with hamster-adapted TME*DY and atypical scrapie.