|Dassanayake, Rohana -|
|Davis, William -|
Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 20, 2012
Publication Date: May 1, 2012
Citation: Dassanayake, R.P., Schneider, D.A., Hoesing, L.M., Truscott, T.C., Davis, W.C., Orourke, K.I. 2012. Cell surface expression of PrP-c and the presence of scrapie prions in the blood of goats. Journal of General Virology. 1127-1131. Interpretive Summary: Classical scrapie is a naturally occurring fatal brain disease of goats and sheep which is caused by prions, a novel class of infectious agent. Presently, laboratory diagnosis of scrapie disease in live animals is limited to the detection of a misfolded form of prion protein (PrP-Sc) in biopsies of certain lymphoid tissues. Although collection of a blood sample for testing would be more convenient and allow more opportunity for repeat testing, the sensitivity for detecting PrP-Sc in blood samples of sheep has been unsuitably low. Furthermore, it is unknown whether scrapie-infected goat blood harbors infectious prions or PrP-Sc. In the research setting, we have confirmed the presence of prions in the peripheral blood of a goat with preclinical scrapie disease. This result suggests it may be possible to develop a diagnostic assay for detecting PrP-Sc in goats. We have also determined that goats express relatively high levels of the normally folded prion protein on the surface of certain peripheral blood mononuclear cells, higher than seen in sheep. Together with similar studies in sheep, these findings should help us develop a sensitive method for detecting PrP-Sc in the blood of goats and sheep with scrapie disease.
Technical Abstract: Classical scrapie is a naturally occurring fatal brain disease of goats and sheep which is caused by prions, a novel class of infectious agent, and is accompanied by the accumulation of abnormal isoforms of prion protein (PrP-Sc) in certain neural and lymphoid tissues. Although collection of a blood sample for live-animal testing would be convenient, the sensitivity of current methods for detecting PrP-Sc in blood samples of sheep has been unsuitably low. In order to improve the sensitivity of current blood-based assays, the objectives of this study were to characterize the distribution of PrP-c in caprine peripheral blood cells and to confirm that prions can be detected within the blood of a naturally infected, preclinical goat. Cell-surface expression of PrP-c was detected on all subsets of goat peripheral blood mononuclear cells but not on polymorphonuclear cells, platelets or red blood cells. The relative cell surface expression of PrP-c on monocytes and subsets of T- and B-lymphocytes were greatest in goats as compared to sheep. As detected by goat bioassay, prions were detected in the whole blood of a preclinical goat with naturally acquired scrapie disease. These results suggest that the blood of goats might be suitable for development of a diagnostic assay. Further studies will be needed, however, to improve the sensitivity of current methodologies through defining which blood cell fractions can be used to enrich the assay for PrP-Sc.