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Transmission Characteristics of Variably Protease-Sensitive Prionopathy

Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (P...

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Detalles Bibliográficos
Autores principales: Notari, Silvio, Xiao, Xiangzhu, Espinosa, Juan Carlos, Cohen, Yvonne, Qing, Liuting, Aguilar-Calvo, Patricia, Kofskey, Diane, Cali, Ignazio, Cracco, Laura, Kong, Qingzhong, Torres, Juan Maria, Zou, Wenquan, Gambetti, Pierluigi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Centers for Disease Control and Prevention 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4257788/
https://www.ncbi.nlm.nih.gov/pubmed/25418590
http://dx.doi.org/10.3201/eid2012.140548
Descripción
Sumario:Variably protease-sensitive prionopathy (VPSPr), a recently identified and seemingly sporadic human prion disease, is distinct from Creutzfeldt-Jakob disease (CJD) but shares features of Gerstmann-Sträussler-Scheinker disease (GSS). However, contrary to exclusively inherited GSS, no prion protein (PrP) gene variations have been detected in VPSPr, suggesting that VPSPr might be the long-sought sporadic form of GSS. The VPSPr atypical features raised the issue of transmissibility, a prototypical property of prion diseases. We inoculated VPSPr brain homogenate into transgenic mice expressing various levels of human PrP (PrP(C)). On first passage, 54% of challenged mice showed histopathologic lesions, and 34% harbored abnormal PrP similar to that of VPSPr. Surprisingly, no prion disease was detected on second passage. We concluded that VPSPr is transmissible; thus, it is an authentic prion disease. However, we speculate that normal human PrP(C) is not an efficient conversion substrate (or mouse brain not a favorable environment) and therefore cannot sustain replication beyond the first passage.