title: Detection and partial discrimination of atypical and classical bovine spongiform encephalopathies in cattle and primates using real-time quaking-induced conversion assay.
abstract: The transmission of classical bovine spongiform encephalopathy (C-BSE) through contaminated meat product consumption is responsible for variant Creutzfeldt-Jakob disease (vCJD) in humans. More recent and atypical forms of BSE (L-BSE and H-BSE) have been identified in cattle since the C-BSE epidemic. Their low incidence and advanced age of onset are compatible with a sporadic origin, as are most cases of Creutzfeldt-Jakob disease (CJD) in humans. Transmissions studies in primates and transgenic mice expressing a human prion protein (PrP) indicated that atypical forms of BSE may be associated with a higher zoonotic potential than classical BSE, and require particular attention for public health. Recently, methods designed to amplify misfolded forms of PrP have emerged as promising tools to detect prion strains and to study their diversity. Here, we validated real-time quaking-induced conversion assay for the discrimination of atypical and classical BSE strains using a large series of bovine samples encompassing all the atypical BSE cases detected by the French Centre of Reference during 10 years of exhaustive active surveillance. We obtained a 100% sensitivity and specificity for atypical BSE detection. In addition, the assay was able to discriminate atypical and classical BSE in non-human primates, and also sporadic CJD and vCJD in humans. The RT-QuIC assay appears as a practical means for a reliable detection of atypical BSE strains in a homologous or heterologous PrP context.
authors.affiliation: Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Levavasseur
authors.affiliation: Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité maladies neuro-dégénératives, Lyon, France.
authors.forename: Anne-Gaëlle
authors.initials: AG
authors.lastname: Biacabe
authors.affiliation: Commissariat à l'Énergie Atomique (CEA), Institut des maladies émergentes et des thérapies nouvelles (IMETI), Service d'étude des prions et des infections atypiques (SEPIA), Fontenay-aux-Roses, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Comoy
authors.affiliation: Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Culeux
authors.affiliation: Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Katarina
authors.initials: K
authors.lastname: Grznarova
authors.affiliation: Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinière, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Privat
authors.affiliation: LFB Biomédicaments, Les Ulis, France.
authors.forename: Steve
authors.initials: S
authors.lastname: Simoneau
authors.affiliation: LFB Biomédicaments, Les Ulis, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Flan
authors.affiliation: AP-HP, Hôpital de la Pitié-Salpêtrière, Neuropathologie, Paris, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Sazdovitch
authors.affiliation: AP-HP, Hôpital de la Pitié-Salpêtrière, Neuropathologie, Paris, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Seilhean
authors.affiliation: Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Unité maladies neuro-dégénératives, Lyon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Baron
authors.affiliation: Inserm U1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris VI UMR S 1127, Institut du Cerveau et de la Moelle épinière, Paris, France.|AP-HP, Hôpital de la Pitié-Salpêtrière, Cellule nationale de référence des MCJ, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Haïk
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D002417:Cattle; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis / Q000473:pathology / Q000662:veterinary*; D016643:Encephalopathy, Bovine Spongiform / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D018419:Primate Diseases / Q000175:diagnosis*; D000072002:Prion Proteins / Q000032:analysis*; D011994:Recombinant Proteins / Q000032:analysis; D012680:Sensitivity and Specificity
chemical_list: D000072002:Prion Proteins; D011994:Recombinant Proteins