title: Prionemia and leukocyte-platelet-associated infectivity in sheep transmissible spongiform encephalopathy models.
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.
authors.affiliation: UMR INRA ENVT 1225, Interactions Hôtes Agents Pathogènes, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lacroux
authors.forename: Didier
authors.initials: D
authors.lastname: Vilette
authors.forename: Natalia
authors.initials: N
authors.lastname: Fernández-Borges
authors.forename: Claire
authors.initials: C
authors.lastname: Litaise
authors.forename: Séverine
authors.initials: S
authors.lastname: Lugan
authors.forename: Nathalie
authors.initials: N
authors.lastname: Morel
authors.forename: Fabien
authors.initials: F
authors.lastname: Corbière
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Simon
authors.forename: Hugh
authors.initials: H
authors.lastname: Simmons
authors.forename: Pierrette
authors.initials: P
authors.lastname: Costes
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Weisbecker
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lantier
authors.forename: Frederic
authors.initials: F
authors.lastname: Lantier
authors.forename: François
authors.initials: F
authors.lastname: Schelcher
authors.forename: Jacques
authors.initials: J
authors.lastname: Grassi
authors.forename: Joaquin
authors.initials: J
authors.lastname: Castilla
authors.forename: Olivier
authors.initials: O
authors.lastname: Andréoletti
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000821:virology*; D004195:Disease Models, Animal; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D051379:Mice; D008822:Mice, Transgenic; D017096:Prion Diseases / Q000635:transmission / Q000662:veterinary* / Q000821:virology*; D012608:Scrapie / Q000635:transmission / Q000821:virology*; D012756:Sheep