Transmission of classical scrapie using lymph node inoculum

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

Submitted to: Research in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/30/2024
Publication Date: 8/1/2024
Citation: Alexis, F.J., West Greenlee, H.M., Bian, J., Greenlee, J.J. 2024. Transmission of classical scrapie using lymph node inoculum. Research in Veterinary Science. https://doi.org/10.1016/j.rvsc.2024.105348.
DOI: https://doi.org/10.1016/j.rvsc.2024.105348

Interpretive Summary: Scrapie is a prion disease that naturally occurs in the sheep population. Prion diseases are invariably fatal neurodegenerative diseases, as there is no cure. The scrapie agent accumulates in a sheep’s brain, affecting their central nervous system, but it also accumulates in the lymph tissues resulting in shedding of prions into the environment. Natural exposure to scrapie occurs through nose-nose contact or through exposure to scrapie prions in the environment. This study was done to understand the infectivity and transmissibility of prions from lymph nodes as compared to those from the brain. Previous work on scrapie has only shown results on clinical disease occurring in sheep through the use of brain material as inoculum. In this study, all sheep inoculated with prions from lymph node or brain developed clinical signs and similar patterns of abnormal prion deposition. This work helps us better understand how scrapie transmits naturally between the sheep. Future work will study the oral inoculation of lymph material into sheep to further understand scrapie transmission. This work is of interest to prion researchers, sheep producers, veterinarians, and those involved with revising regulations for scrapie control.

Technical Abstract: Scrapie is a fatal, easily transmissible neurodegenerative disease that affects sheep and goats. The scrapie agent travels throughout a sheep’s lymphatic system prior to neuroinvasion. Replication of PrPSc in the lymphoid tissue allows for the scrapie agent to be easily shed into the environment. Brain and retropharyngeal lymph node (RPLN) material derived from a sheep inoculated with the classical scrapie agent (13-7) was used to determine if lymph node material is infectious when inoculated into sheep intracranially. Ten Cheviot sheep were used in this study, randomly assigned into two groups based on inoculum material. Group one (n=4) received 1 mL of 10% brain homogenate (13-7) and consisted of all VRQ genotypes at the PRNP gene. Group two (n=6) had four sheep receive 1 mL of a 10% RPLN homogenate (13-7), and two sheep receive 0.5 mL of a 10% RPLN homogenate (13-7). Sheep in group two were also VRQ genotyped at the PRNP gene, while one sheep was AVRQ. Brain and lymph tissues were tested by histopathology, immunohistochemistry, western blot, enzyme immunoassay, and conformational stability for PrPSc accumulation. Both groups displayed clinical signs of ataxia, moribund, head tremors, and lethargy prior to euthanizing at an average of 16.2 mpi (months post inoculation) (group one) and 19.1 mpi (group two). Additionally, brainstem tissue from both groups displayed the same apparent molecular mass. Pathology results indicated similar spongiform lesion profiling, as well as PrPSc accumulation between brain and lymph tissues within both groups. Conformational stability results displayed no significant difference in obex or RPLN tissue. Overall, these data suggest lymph nodes containing the classical scrapie agent are infectious to sheep, aiding in the understanding of sheep scrapie transmission.