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

Abstract

Prion diseases are neurodegenerative diseases characterized by the accumulation of misfolded prion protein (PrPSc) 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. We investigated the susceptibility of raccoons to various prion disease agents and compared the clinicopathologic features of the resulting disease. Raccoon kits were inoculated intracranially with the agents of raccoon-passaged TME (TMERac), bovine-passaged TME (TMEBov), hamster-adapted drowsy (TMEDY) or hyper TME (TMEHY), CWD from white-tailed deer (CWDWtd) or elk (CWDElk), or atypical (Nor98) scrapie. Raccoons were euthanized when they developed clinical signs of prion disease or at study endpoint (<82 mo post-inoculation). Brain was examined for the presence of spongiform change, and disease-associated PrPSc was detected using an enzyme immunoassay, western blot, and immunohistochemistry. All raccoons inoculated with the agents of TMERac and TMEBov developed clinical disease at ~6.6 mo post-inoculation, with widespread PrPSc accumulation in central nervous system tissues. PrPSc was detected in the brain of 1 of 4 raccoons in each of the CWDWtd-, CWDElk-, and TMEHY-inoculated groups. None of the raccoons inoculated with TMEDY or atypical scrapie agents developed clinical disease or detectable PrPSc accumulation. Our results indicate that raccoons are highly susceptible to infection with raccoon- and bovine-passaged TME agents, whereas CWD isolates from white-tailed deer or elk and hamster-adapted TMEHY transmit poorly. Raccoons appear to be resistant to infection with hamster-adapted TMEDY and atypical scrapie agents.