Location: Virus and Prion ResearchTitle: The chronic wasting disease agent from mule deer has widespread lymphoid distribution in sheep after second passage intracranial inoculation
|CASSMANN, ERIC - Oak Ridge Institute For Science And Education (ORISE)|
Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 8/30/2019
Publication Date: N/A
Technical Abstract: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy characterized by fatal neurodegeneration and wasting in cervids. The disease is associated with the accumulation of misfolded prion protein (PrPSc). We previously demonstrated that sheep were susceptible to the agent of chronic wasting disease from mule deer (CWDmd) after intracranial inoculation. A sheep with the V136R154Q171/ARQ genotype demonstrated clinical disease and had detectable PrPSc in the brain, tonsils, lymph nodes, and limited amounts in the spleen after a 35-month incubation period (IP). The objective of the present experiment was to further explore the permissiveness of PrPSc lymphoid replication and tissue distribution in sheep with different genotypes after passage of VRQ/ARQ brain inoculum. Sheep with the VRQ/ARQ (n=6), ARQ/ARQ (n=4), and ARQ/ARR (n=2) PRNP genotypes were intracranially inoculated with 100 mg tissue equivalent of brain homogenate from a VRQ/ARQ sheep that had received the agent of CWDmd. Sheep of all genotypes had PrPSc accumulation with IPs of 14.6 months (VRQ/ARQ), 11.3 months (ARQ/ARQ), and 60 months (ARQ/ARR). PrPSc was detected in their brains by immunohistochemistry, enzyme immunoassay, and western blot analysis. In sheep with the VRQ/ARQ and ARQ/ARQ genotypes, there was widespread dissemination of PrPSc in the lymphoid tissues including the tonsils, lymph nodes, spleen, Peyer’s patches, and rectal mucosa. These results demonstrate that sheep are permissive to PrPSc replication in the brain and lymphoid tissue after interspecies transmission of the agent of CWDmd; unexpectedly, sheep with the ARQ/ARQ genotype had a shorter incubation period than VRQ/ARQ genotype sheep.