Spontaneous generation of mammalian prions
- 26 July 2010
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 107 (32), 14402-14406
- https://doi.org/10.1073/pnas.1004036107
Abstract
Prions are transmissible agents that cause lethal neurodegeneration in humans and other mammals. Prions bind avidly to metal surfaces such as steel wires and, when surface-bound, can initiate infection of brain or cultured cells with remarkable efficiency. While investigating the properties of metal-bound prions by using the scrapie cell assay to measure infectivity, we observed, at low frequency, positive assay results in control groups in which metal wires had been coated with uninfected mouse brain homogenate. This phenomenon proved to be reproducible in rigorous and exhaustive control experiments designed to exclude prion contamination. The infectivity generated in cell culture could be readily transferred to mice and had strain characteristics distinct from the mouse-adapted prion strains used in the laboratory. The apparent ”spontaneous generation” of prions from normal brain tissue could result if the metal surface, possibly with bound cofactors, catalyzed de novo formation of prions from normal cellular prion protein. Alternatively, if prions were naturally present in the brain at levels not detectable by conventional methods, metal surfaces might concentrate them to the extent that they become quantifiable by the scrapie cell assay.Keywords
This publication has 33 references indexed in Scilit:
- Generating a Prion with Bacterially Expressed Recombinant Prion ProteinScience, 2010
- Darwinian Evolution of Prions in Cell CultureScience, 2010
- Prion Strain Discrimination Based on Rapid In Vivo Amplification and Analysis by the Cell Panel AssayPLOS ONE, 2009
- De Novo Generation of Infectious Prions In Vitro Produces a New Disease PhenotypePLoS Pathogens, 2009
- Highly sensitive, quantitative cell-based assay for prions adsorbed to solid surfacesProceedings of the National Academy of Sciences, 2009
- Detection and characterization of proteinase K-sensitive disease-related prion protein with thermolysinBiochemical Journal, 2008
- Prion strain discrimination in cell culture: The cell panel assayProceedings of the National Academy of Sciences, 2007
- Formation of native prions from minimal components in vitroProceedings of the National Academy of Sciences, 2007
- Aggregation of cellular prion protein is initiated by proximity‐induced dimerizationJournal of Neurochemistry, 2007
- Continuum of prion protein structures enciphers a multitude of prion isolate-specified phenotypesProceedings of the National Academy of Sciences, 2006