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Title: Accumulation of PrP-Sc in hemal nodes of naturally and experimentally scrapie-infected sheep

Author
item DASSANAYAKE, ROHANA - Washington State University
item Truscott, Thomas
item ÖZYIGIT, ÖZGÜR - Uludag University
item Zhuang, Dongyue
item Schneider, David
item O'ROURKE, KATHERINE - Washington State University

Submitted to: BioMed Central (BMC) Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/2013
Publication Date: 4/19/2013
Publication URL: https://handle.nal.usda.gov/10113/56589
Citation: Dassanayake, R.P., Truscott, T.C., Özyigit, Ö.M., Zhuang, D., Schneider, D.A., O'Rourke, K.I. 2013. Accumulation of PrP-Sc in hemal nodes of naturally and experimentally scrapie-infected sheep. BioMed Central (BMC) Veterinary Research. doi:10.1186/1746-6148-9-82.

Interpretive Summary: Classical scrapie is a naturally occurring fatal disease of sheep and goats which is caused by prions, a novel class of infectious agent. Presently, laboratory diagnosis of scrapie disease in live animals is limited to detection of a disease-associated form of prion protein (PrP-Sc) in lymphoid tissues accessible to biopsy. Recent studies done by us and others, however, demonstrate the presence of the infectious agent in the blood, suggesting cellular components of the blood may be a suitable basis from which to develop of a new live animal test. To further investigate this possibility in sheep, we examined the accumulation of PrP-Sc in cells of hemal nodes—unique lymphoid structures of ruminants that, unlike lymph nodes, derive its cellular composition from the blood rather than lymph. Cellular accumulation of PrP-Sc in hemal nodes occurred early during preclinical disease and, despite the anatomic differences between hemal and lymph nodes, was characteristic of that accumulating in lymph nodes. These findings are consistent with the early presence of prions in the blood of infected sheep and further support the possibility of developing a blood-based diagnostic test for scrapie disease in live animals with preclinical infection.

Technical Abstract: Classical scrapie is a naturally occurring fatal disease of sheep and goats which is caused by prions, a novel class of infectious agent. Infection is accompanied by accumulation of abnormal isoforms of the prion protein (PrP-Sc) in certain neural and lymphoid tissues. Hemal nodes, which are unique lymphoid structures found along large blood vessels of ruminants, lack a lymphatic circulatory system and instead receive leukocytes only from the blood. Hemal nodes are likely to accumulate PrP-Sc since certain cellular components of the blood are now known to harbor prions. However, the cellular distribution and molecular processing of PrP-Sc in hemal nodes is not known. Therefore, the objectives of this study were to compare the cellular distribution and molecular processing of the PrP-Sc accumulating in hemal nodes and retropharyngeal lymph nodes collected from naturally and experimentally (blood transfusion) scrapie-infected sheep. Out of 84 sheep confirmed to be scrapie-infected by standard immunohistochemical detection of PrP-Sc in the retropharyngeal lymph node, hemal node accumulation of PrP-Sc was detected in 66 animals (79%). In both tissue types, co-labeling using cell type-specific and prion protein-specific antibodies revealed that PrP-Sc accumulation was mostly confined to macrophages and follicular dendritic cells. Cellular processing of PrP-Sc was investigated by epitope mapping using antibodies specific for the N-terminus (n=4), central (n=2) and C-terminus (n=1) regions of the prion protein. No differences in labeling patterns were noted between the epitope-specific antibodies or between tissues types. Thus, we conclude that the cellular accumulation and processing of PrP-Sc derived from the blood in hemal nodes are similar to that occurring in lymph nodes. These findings are consistent with the early presence of prions in the blood of infected sheep and further support the possibility of developing a blood-based diagnostic test for scrapie disease in live animals with preclinical sheep.