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Journals Journal of Virology Volume 86 Issue 4

Prionemia and Leukocyte-Platelet-Associated Infectivity in Sheep Transmissible Spongiform Encephalopathy Models Caroline Lacroux a , Didier Vilette a , Natalia Fernández-Borges b , Claire Litaise a , Séverine Lugan a , Nathalie Morel d , Fabien Corbière a , Stéphanie Simon d , Hugh Simmons e , Pierrette Costes a , Jean-Louis Weisbecker f , Isabelle Lantier g , Frederic Lantier g , François Schelcher a , Jacques Grassi d , Joaquin Castilla b , c and Olivier Andréoletti a a UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France b CIC bioGUNE, Parque Tecnológico de Bizkaia, Derio, Spain c IKERBASQUE, Basque Foundation for Science, Bilbao, Spain d CEA, Service de Pharmacologie et d'Immunoanalyse, IBiTec-S, DSV, CEA/Saclay, Gif sur Yvette, France e VLA Weybridge, ASU, New Haw, Addlestone, Surrey, United Kingdom f INRA Domaine de Langlade, Pompertuzat, France g INRA IASP, Centre INRA de Tours, Nouzilly, France ABSTRACT 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 10 6.5 -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.

Prionemia and Leukocyte-Platelet-Associated Infectivity in Sheep Transmissible Spongiform Encephalopathy Models

Abstract

Prionemia and Leukocyte-Platelet-Associated Infectivity in Sheep Transmissible Spongiform Encephalopathy Models Caroline Lacroux a , Didier Vilette a , Natalia Fernández-Borges b , Claire Litaise a , Séverine Lugan a , Nathalie Morel d , Fabien Corbière a , Stéphanie Simon d , Hugh Simmons e , Pierrette Costes a , Jean-Louis Weisbecker f , Isabelle Lantier g , Frederic Lantier g , François Schelcher a , Jacques Grassi d , Joaquin Castilla b , c and Olivier Andréoletti a a UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France b CIC bioGUNE, Parque Tecnológico de Bizkaia, Derio, Spain c IKERBASQUE, Basque Foundation for Science, Bilbao, Spain d CEA, Service de Pharmacologie et d'Immunoanalyse, IBiTec-S, DSV, CEA/Saclay, Gif sur Yvette, France e VLA Weybridge, ASU, New Haw, Addlestone, Surrey, United Kingdom f INRA Domaine de Langlade, Pompertuzat, France g INRA IASP, Centre INRA de Tours, Nouzilly, France ABSTRACT 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 10 6.5 -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.

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Prionemia and Leukocyte-Platelet-Associated Infectivity in Sheep Transmissible Spongiform Encephalopathy Models

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  • Publisher American Society for Microbiology
  • Copyright Copyright © 2012 by the American society for Microbiology.
  • ISSN 0022-538X
  • eISSN 1098-5514
  • D.O.I. 10.1128/JVI.06532-11
  • Publisher site Get PDF  

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