Assessment of the Zoonotic Potential of Atypical Scrapie Prions in Humanized Mice Reveals Rare Phenotypic Convergence but Not Identity With Sporadic Creutzfeldt-Jakob Disease Prions.

BACKGROUND: Atypical/Nor98 scrapie (AS) is an idiopathic infectious prion disease affecting sheep and goats. Recent findings suggest that zoonotic prions from classical bovine spongiform encephalopathy (C-BSE) may copropagate with atypical/Nor98 prions in AS sheep brains. Investigating the risk AS poses to humans is crucial. METHODS: To assess the risk of sheep/goat-to-human transmission of AS, we serially inoculated brain tissue from field and laboratory isolates into transgenic mice overexpressing human prion protein (Met129 allele). We studied clinical outcomes as well as presence of prions in brains and spleens. RESULTS: No transmission occurred on the primary passage, with no clinical disease or pathological prion protein in brains and spleens. On subsequent passages, 1 isolate gradually adapted, manifesting as prions with a phenotype resembling those causing MM1-type sporadic Creutzfeldt-Jakob disease in humans. However, further characterization using in vivo and in vitro techniques confirmed both prion agents as different strains, revealing a case of phenotypic convergence. Importantly, no C-BSE prions emerged in these mice, especially in the spleen, which is more permissive than the brain for C-BSE cross-species transmission. CONCLUSIONS: The results obtained suggest a low zoonotic potential for AS. Rare adaptation may allow the emergence of prions phenotypically resembling those spontaneously forming in humans.

[Clinical characteristics and diagnostics of human spongiform encephalopathies: an update]. / Klinik und Diagnostik humaner spongiformer Enzephalopathien: ein Update.

Human spongiform encephalopathies are rare transmissible neurodegenerative diseases of the brain and the nervous system that are caused by misfolding of the physiological prion protein into a pathological form and its deposition in the central nervous system (CNS). Prion diseases include Creutzfeldt-Jakob disease (CJD, sporadic or familial), Gerstmann-Straussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI). Prion diseases can be differentiated into three etiological categories: spontaneous (sporadic CJD), inherited (familial CJD, FFI, and GSS) and acquired (variant CJD and iatrogenic CJD). Most cases occur sporadically. Prion diseases can lead to a variety of neurological symptoms and always have an inevitably fatal course. Cerebrospinal fluid analysis and magnetic resonance imaging (MRI) play a crucial role in the diagnostics of prion diseases and may facilitate an early and reliable clinical diagnosis. A causal treatment or specific therapeutic agents are not yet available. In general, a palliative therapeutic concept is indicated.

Expresión y localización de la proteína priónica celular (PrPC) en el sistema nervioso central de la vaca. Algunas reflexiones sobre la nvCJD / Expression and localization of the cellular prion protein (PrPc) in the cow's central nervous system. Some reflections on the nvCJD

Introducción. La repercusión económica y social de la encefalopatía espongiforme bovina (EEB) y su relación con la nueva variante de la enfermedad de Creutzfeldt-Jakob (nvCJD) hace interesante un estudio de la expresión y localización de la proteína priónica celular (PrPC) en el sistema nervioso central de la vaca, con especial atención al tronco del encéfalo, especialmente alterado en la EEB. Según varios autores la presencia PrPC es esencial para el establecimiento y replicación del prión (PrPSc), presente en la EEB. Material y métodos. Se utilizaron muestras de encéfalos de vacas de raza autóctona pirenaica. Se estudió la expresión de PrP mediante técnicas de wester blot, así como la localización de PrPC en el sistema nervioso central, con especial atención al tronco del encéfalo. Resultados. La expresión y cuantificación de PrP fue mayor en zonas rostrales que en caudales. La inmunohistoquímica fue concordante con el western. La localización de PrPC era importante en corteza cerebral, hipocampo, etc. Se destacó inmunopositividad notable en el núcleo motor dorsal del nervio vago y en el del nervio hipogloso. El asta anterior de la médula cervical era más inmunopositiva que el asta posterior. Conclusión. Existe una mayor abundancia de PrPC en zonas rostrales que en caudales del sistema nervioso central de la vaca. Debido a la presencia de PrPC en neuronas motoras, y de acuerdo con hallazgos en otras especies de mamíferos, la transmisión de la PrPSc se haría retrógradamente desde su vía de acceso y en el interior del sistema nervioso central (AU)

Introduction: The appearance of bovine spongiform encephalopathy (BSE) and its involvement in the generation of the new variant of Creutzfeldt-Jakob Disease (nvCJD) had important implications from a social and economical point of view. As the presence of PrPC is necessary to establish prion diseases and for the replication of PrPSC in BSE, the study of the expression and localization of PrPC in the central nervous system of cow, mainly the brainstem, is interesting itself. Material and methods: Expression of PrP by western blot technique and its precise localization by immunohistochemistry were analyzed in the central nervous system of the autochthonous pyrenees breed, a group of cows with a high incidence for BSE. Results: PrP was more abundantly expressed in rostral areas rather than caudal regions of the cow brain. Immunohistochemistry was congruent with western blotting studies. Localization of PrPC was particularly abundant in the cerebral cortex, hippocampus, etc. Noteworthy, immunopositivity was present in the dorsal motor nucleus of the vagus and the hypoglossal nucleus. The anterior horn of the spinal cord yielded higher labelling for PrP than the posterior horn. Conclusion: PrPC is more abundantly expressed in rostral areas of the central nervous system. According to the findings observed in other mammal species, presence of PrPC in motoneurons of cow indicates that PrPSc might be transported from its site of entry to the central nervous system following a retrograde direction (AU)

El patólogo ante las encefalopatías espongiformes transmisibles / No disponible

No disponible

Bicentenario de la Real Expedición Filantrópica de la Vacuna, 1803 a 1806-2003 a 2006 / No disponible

No disponible

Protección sanitaria biológica: seguridad alimentaria / No disponible

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Caderno técnico: encefalopatia espongiforme transmissível / Technical notebook: TSE

A nova variante da Doença de Creutzfeld-Jakob, cuja origem é atribuida à ingestão de produtos de origem animal - especialmente bovino - contendo a proteína priônica, traz novos desafios a cientistas e profissionais de saúde pública.