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Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains


Prion diseases are neurodegenerative disorders that propagate as multiple strains in a variety of mammalian species. The detection of all such prion types by a single ultrasensitive assay, such as the Real Time Quaking-induced Conversion (RT-QuIC) assay, would facilitate prion disease diagnosis, surveillance, and research. Here we show detection of minute amounts of 28 different prion types from humans, cattle, sheep, cervids and rodents, some of which were previously undetectable, using a single recombinant bank vole prion protein substrate. We also demonstrate the generation of prion type-dependent RT-QuIC conversion products which may help with prion strain discrimination and the characterization of distinct classes of prion templates. Finally, we describe a practical strategy for prion strain discrimination, e.g. classical and atypical L-type bovine spongiform encephalopathy; classical and atypical Nor98 sheep scrapie; and human sporadic and variant Creutzfeldt-Jakob disease. Thus, our study provides a basis for wide-ranging prion detection and strain discrimination.


Vyšlo v časopise: Bank Vole Prion Protein As an Apparently Universal Substrate for RT-QuIC-Based Detection and Discrimination of Prion Strains. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004983
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004983

Souhrn

Prion diseases are neurodegenerative disorders that propagate as multiple strains in a variety of mammalian species. The detection of all such prion types by a single ultrasensitive assay, such as the Real Time Quaking-induced Conversion (RT-QuIC) assay, would facilitate prion disease diagnosis, surveillance, and research. Here we show detection of minute amounts of 28 different prion types from humans, cattle, sheep, cervids and rodents, some of which were previously undetectable, using a single recombinant bank vole prion protein substrate. We also demonstrate the generation of prion type-dependent RT-QuIC conversion products which may help with prion strain discrimination and the characterization of distinct classes of prion templates. Finally, we describe a practical strategy for prion strain discrimination, e.g. classical and atypical L-type bovine spongiform encephalopathy; classical and atypical Nor98 sheep scrapie; and human sporadic and variant Creutzfeldt-Jakob disease. Thus, our study provides a basis for wide-ranging prion detection and strain discrimination.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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