It appears you don't have support to open PDFs in this web browser. To view this file, Open with your PDF reader
Abstract
Unlike variant Creutzfeldt–Jakob disease prions, sporadic Creutzfeldt–Jakob disease prions have been shown to be difficult to amplify in vitro by protein misfolding cyclic amplification (PMCA). We assessed PMCA of pathological prion protein (PrPTSE) from 14 human sCJD brain samples in 3 substrates: 2 from transgenic mice expressing human prion protein (PrP) with either methionine (M) or valine (V) at position 129, and 1 from bank voles. Brain extracts representing the 5 major clinicopathological sCJD subtypes (MM1/MV1, MM2, MV2, VV1, and VV2) all triggered seeded PrPTSE amplification during serial PMCA with strong seed- and substrate-dependence. Remarkably, bank vole PrP substrate allowed the propagation of all sCJD subtypes with preservation of the initial molecular PrPTSE type. In contrast, PMCA in human PrP substrates was accompanied by a PrPTSE molecular shift during heterologous (M/V129) PMCA reactions, with increased permissiveness of V129 PrP substrate to in vitro sCJD prion amplification compared to M129 PrP substrate. Combining PMCA amplification sensitivities with PrPTSE electrophoretic profiles obtained in the different substrates confirmed the classification of 4 distinct major sCJD prion strains (M1, M2, V1, and V2). Finally, the level of sensitivity required to detect VV2 sCJD prions in cerebrospinal fluid was achieved.
You have requested "on-the-fly" machine translation of selected content from our databases. This functionality is provided solely for your convenience and is in no way intended to replace human translation. Show full disclaimer
Neither ProQuest nor its licensors make any representations or warranties with respect to the translations. The translations are automatically generated "AS IS" and "AS AVAILABLE" and are not retained in our systems. PROQUEST AND ITS LICENSORS SPECIFICALLY DISCLAIM ANY AND ALL EXPRESS OR IMPLIED WARRANTIES, INCLUDING WITHOUT LIMITATION, ANY WARRANTIES FOR AVAILABILITY, ACCURACY, TIMELINESS, COMPLETENESS, NON-INFRINGMENT, MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. Your use of the translations is subject to all use restrictions contained in your Electronic Products License Agreement and by using the translation functionality you agree to forgo any and all claims against ProQuest or its licensors for your use of the translation functionality and any output derived there from. Hide full disclaimer
Details
1 Université de Montpellier, Pathogenesis and Control of Chronic Infections, Etablissement Français du Sang, Inserm, Montpellier, France (GRID:grid.121334.6) (ISNI:0000 0001 2097 0141)
2 Istituto Superiore di Sanita, Department of Food Safety, Nutrition and Veterinary Public Health, Rome, Italy (GRID:grid.416651.1) (ISNI:0000 0000 9120 6856)
3 Sorbonne Universités, Inserm U 1127, CNRS UMR 7225, UPMC Université Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, Paris, France (GRID:grid.462844.8) (ISNI:0000 0001 2308 1657)
4 University of Toronto, Tanz Centre for Research in Neurodegenerative Diseases and Department of Biochemistry, Toronto, Canada (GRID:grid.17063.33) (ISNI:0000 0001 2157 2938)
5 Univ Montpellier, IRMB, INM, INSERM, CHU Montpellier, (LBPC-PPC), Montpellier, France (GRID:grid.121334.6) (ISNI:0000 0001 2097 0141)