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Title: Classical scrapie prions are associated with peripheral blood monocytes and T-lymphocytes from naturally infected sheep

Author
item DASSANAYKE, ROHANA - Washington State University
item MADSEN-BOUTERSE, SALLY - Washington State University
item Truscott, Thomas
item Zhuang, Dongyue
item Mousel, Michelle
item DAVIS, WILLIAM - Washington State University
item Schneider, David

Submitted to: BioMed Central (BMC) Veterinary Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/31/2016
Publication Date: 2/4/2016
Citation: Dassanayke, R.P., Madsen-Bouterse, S.A., Truscott, T.C., Zhuang, D., Mousel, M.R., Davis, W.C., Schneider, D.A. 2016. Classical scrapie prions are associated with peripheral blood monocytes and T-lymphocytes from naturally infected sheep. BioMed Central (BMC) Veterinary Research. doi: 10.1186/s12917-016-0651-6.

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. Diagnosis of scrapie disease in live animals is limited to detection of a disease-associated form of the prion protein in lymphoid tissues accessible to biopsy. Recent studies done by us and others, however, demonstrate the presence of scrapie prions in the blood, suggesting certain cellular blood components may be a suitable basis for developing a new live animal test. We now report on the association of scrapie prions with two additional types of blood cells from infected sheep. Collectively, the results of these studies clarify which cellular fractions are suitable targets for development of a blood-based live animal test for classical scrapie infection in sheep.

Technical Abstract: Classical scrapie is a transmissible spongiform encephalopathy that affects sheep and goats. As detected by enzyme-linked immunoassay, previous studies suggested scrapie prions in the blood of sheep might be associated with B lymphocytes but not with monocytes or T lymphocytes. The association of scrapie prions with circulating B lymphocytes was confirmed by bioassay in lambs and transgenic mice. Because bioassay is more sensitive than immunoassay, the objective of the present study was to similarly determine if scrapie prions are associated with circulating monocytes and T lymphocytes. To do this, peripheral blood mononuclear cells (PBMC), monocytes, and T lymphocytes were separately isolated from two pre-clinical VRQ/VRQ sheep naturally infected with classical scrapie. Each type of cellular blood fraction was intravenously transfused into VRQ/VRQ recipient lambs. Infections status was monitored by antemortem rectal biopsy and final postmortem examination through the detection of disease-associated prion protein (PrP-Sc) by standard scrapie immunohistochemistry. Transmission of infection was detected in 4 of 4 lambs receiving PBMC, in 2 of 5 lambs receiving monocytes, and in 1 of 4 lambs receiving T lymphocytes. Furthermore, we tested PMBC isolated from some of the recipient sheep just prior to euthanasia for the presence of prion protein misfolding activity as detected by serial protein misfolding cyclic amplification (sPMCA). Prion protein misfolding activity was detected in sheep previously inoculated with either the monocyte or T lymphocyte blood fraction in complete concordance with the infection status as determined at postmortem examination. In conclusion, the findings demonstrate that monocytes and T lymphocytes, in addition to B lymphocytes, can harbor classical scrapie prions in the blood of sheep during preclinical infection. The findings support the conclusion that all PBMC may be a suitable blood fraction to target in the development of a highly-sensitive in vitro, blood-based diagnostic test for preclinical detection of classical scrapie in sheep.