Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

Abstract

BackgroundClassical scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats characterized by cellular accumulation of abnormal isoforms of prion protein (PrPSc) in the central nervous system and the follicles of peripheral lymphoid tissues. Previous studies have shown that the whole blood and buffy coat blood fraction of scrapie infected sheep harbor prion infectivity. Although PrPSc has been detected in peripheral blood mononuclear cells (PBMCs), plasma, and more recently within a subpopulation of B lymphocytes, the infectivity status of these cells and plasma in sheep remains unknown. Therefore, the objective of this study was to determine whether circulating PBMCs, B lymphocytes and platelets from classical scrapie infected sheep harbor prion infectivity using a sheep bioassay.ResultsSerial rectal mucosal biopsy and immunohistochemistry were used to detect preclinical infection in lambs transfused with whole blood or blood cell fractions from preclinical or clinical scrapie infected sheep. PrPSc immunolabeling was detected in antemortem rectal and postmortem lymphoid tissues from recipient lambs receiving PBMCs (15/15), CD72+ B lymphocytes (3/3), CD21+ B lymphocytes (3/3) or platelet-rich plasma (2/3) fractions. As expected, whole blood (11/13) and buffy coat (5/5) recipients showed positive PrPSc labeling in lymphoid follicles. However, at 549 days post-transfusion, PrPSc was not detected in rectal or other lymphoid tissues in three sheep receiving platelet-poor plasma fraction.ConclusionsPrion infectivity was detected in circulating PBMCs, CD72+ pan B lymphocytes, the CD21+ subpopulation of B lymphocytes and platelet-rich plasma of classical scrapie infected sheep using a sheep bioassay. Combining platelets with B lymphocytes might enhance PrPSc detection levels in blood samples.

Clinical, haematological and biochemical responses of sheep undergoing autologous blood transfusion

“…The use of autologous transfusion has the advantage of eliminating the risk of immune-mediated haemolytic reactions, virus and prion transmission, febrile reactions, and allergic reactions and reduces the risk of postoperative infection and incidence of cancer that can occur in homologous transfusions due to immune system modulation [4,5]. …”

Accumulation profiles of PrPSc in hemal nodes of naturally and experimentally scrapie-infected sheep

“…Lambs became scrapie infected either through natural exposure or by intravenous transfusion of whole blood or blood cell fractions isolated from scrapie-infected sheep [13]. Transmission of scrapie was confirmed by rectal biopsy [13].…”

“…Transmission of scrapie was confirmed by rectal biopsy [13]. Postmortem tissues were collected at both preclinical and clinical time points and routinely processed for scrapie IHC [9].…”

Prion and prion-like diseases in animals

“…Besides, the presence of scrapie infectivity in blood (Bannach et al, 2012;Dassanayake et al, 2011Dassanayake et al, , 2012Lacroux et al, 2012), saliva (Gough et al, 2011;Tamguney et al, 2012), milk (Ligios et al, 2011) and colostum (Konold et al, 2013) in conjunction with the high resistance of this prion agent against denaturizing factors contributes to its permanency in the environment, i.e. in soil (Saunders et al, 2012b), and consequently favors the horizontal transmission within sheep and goats herds.…”