Prionemia and Leukocyte-Platelet-Associated Infectivity in Sheep Transmissible Spongiform Encephalopathy Models
Caroline Lacrouxa, Didier Vilettea, Natalia Fernández-Borgesb, Claire Litaisea, Séverine Lugana, Nathalie Moreld, Fabien Corbièrea, Stéphanie Simond, Hugh Simmonse, Pierrette Costesa, Jean-Louis Weisbeckerf, Isabelle Lantierg, Frederic Lantierg, François Schelchera, Jacques Grassid, Joaquin Castillab,c and Olivier Andréolettia
+ Author Affiliations
aUMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France
bCIC bioGUNE, Parque Tecnológico de Bizkaia, Derio, Spain
cIKERBASQUE, Basque Foundation for Science, Bilbao, Spain
dCEA, Service de Pharmacologie et d'Immunoanalyse, IBiTec-S, DSV, CEA/Saclay, Gif sur Yvette, France
eVLA Weybridge, ASU, New Haw, Addlestone, Surrey, United Kingdom
fINRA Domaine de Langlade, Pompertuzat, France
gINRA IASP, Centre INRA de Tours, Nouzilly, France
The dynamics of the circulation and distribution of transmissible spongiform encephalopathy (TSE) agents in the blood of infected individuals remain largely unknown. This clearly limits the understanding of the role of blood in TSE pathogenesis and the development of a reliable TSE blood detection assay. Using two distinct sheep scrapie models and blood transfusion, this work demonstrates the occurrence of a very early and persistent prionemia. This ability to transmit disease by blood transfusion was correlated with the presence of infectivity in white blood cells (WBC) and peripheral blood mononucleated cells (PBMC) as detected by bioassay in mice overexpressing the ovine prion protein PrP (tg338 mice) and with the identification of abnormal PrP in WBC after using protein misfolding cyclic amplification (PMCA). Platelets and a large variety of leukocyte subpopulations also were shown to be infectious. The use of endpoint titration in tg338 mice indicated that the infectivity in WBC (per ml of blood) was 106.5-fold lower than that in 1 g of posterior brainstem sample. In both WBC and brainstem, infectivity displayed similar resistance to PK digestion. The data strongly support the concept that WBC are an accurate target for reliable TSE detection by PMCA. The presence of infectivity in short-life-span blood cellular elements raises the question of the origin of prionemia.
FOOTNOTES Received 11 October 2011. Accepted 18 November 2011. Address correspondence to O. Andreoletti, email@example.com.
Published ahead of print 7 December 2011
Copyright © 2012, American Society for Microbiology. All Rights Reserved.
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Labels: Prionemia and Leukocyte-Platelet-Associated Infectivity in Sheep Transmissible Spongiform Encephalopathy Models