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Relationships between PrP(Sc) Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System
Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP(C)) into a â-rich conformer (PrP(Sc)) that accumulates into higher-order structures in the brain and other tissu...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2012
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419241/ https://www.ncbi.nlm.nih.gov/pubmed/22916207 http://dx.doi.org/10.1371/journal.pone.0043060 |
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author | Vrentas, Catherine E. Greenlee, Justin J. Tatum, Trudy L. Nicholson, Eric M. |
author_facet | Vrentas, Catherine E. Greenlee, Justin J. Tatum, Trudy L. Nicholson, Eric M. |
author_sort | Vrentas, Catherine E. |
collection | PubMed |
description | Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP(C)) into a â-rich conformer (PrP(Sc)) that accumulates into higher-order structures in the brain and other tissues. Distinct strains of TSEs exist, characterized by different pathologic profiles upon passage into rodents and representing distinct conformations of PrP(Sc). One biochemical method of distinguishing strains is the stability of PrP(Sc) as determined by unfolding in guanidine hydrochloride (GdnHCl), which is tightly and positively correlated with the incubation time of disease upon passage into mice. Here, we utilize a rapid, protease-free version of the stability assay to characterize naturally occurring scrapie samples, including a fast-acting scrapie inoculum for which incubation time is highly dependent on the amino acid at codon 136 of the prion protein. We utilize the stability methodology to identify the presence of two distinct isolates in the inoculum, and compare isolate properties to those of a host-stabilized reference scrapie isolate (NADC 13-7) in order to assess the stability/incubation time correlation in a natural host system. We demonstrate the utility of the stability methodology in characterizing TSE isolates throughout serial passage in livestock, which is applicable to a range of natural host systems, including strains of bovine spongiform encephalopathy and chronic wasting disease. |
format | Online Article Text |
id | pubmed-3419241 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34192412012-08-22 Relationships between PrP(Sc) Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System Vrentas, Catherine E. Greenlee, Justin J. Tatum, Trudy L. Nicholson, Eric M. PLoS One Research Article Transmissible spongiform encephalopathies (TSEs), including scrapie in sheep (Ovis aries), are fatal neurodegenerative diseases caused by the misfolding of the cellular prion protein (PrP(C)) into a â-rich conformer (PrP(Sc)) that accumulates into higher-order structures in the brain and other tissues. Distinct strains of TSEs exist, characterized by different pathologic profiles upon passage into rodents and representing distinct conformations of PrP(Sc). One biochemical method of distinguishing strains is the stability of PrP(Sc) as determined by unfolding in guanidine hydrochloride (GdnHCl), which is tightly and positively correlated with the incubation time of disease upon passage into mice. Here, we utilize a rapid, protease-free version of the stability assay to characterize naturally occurring scrapie samples, including a fast-acting scrapie inoculum for which incubation time is highly dependent on the amino acid at codon 136 of the prion protein. We utilize the stability methodology to identify the presence of two distinct isolates in the inoculum, and compare isolate properties to those of a host-stabilized reference scrapie isolate (NADC 13-7) in order to assess the stability/incubation time correlation in a natural host system. We demonstrate the utility of the stability methodology in characterizing TSE isolates throughout serial passage in livestock, which is applicable to a range of natural host systems, including strains of bovine spongiform encephalopathy and chronic wasting disease. Public Library of Science 2012-08-14 /pmc/articles/PMC3419241/ /pubmed/22916207 http://dx.doi.org/10.1371/journal.pone.0043060 Text en © 2012 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Vrentas, Catherine E. Greenlee, Justin J. Tatum, Trudy L. Nicholson, Eric M. Relationships between PrP(Sc) Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System |
title | Relationships between PrP(Sc) Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System |
title_full | Relationships between PrP(Sc) Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System |
title_fullStr | Relationships between PrP(Sc) Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System |
title_full_unstemmed | Relationships between PrP(Sc) Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System |
title_short | Relationships between PrP(Sc) Stability and Incubation Time for United States Scrapie Isolates in a Natural Host System |
title_sort | relationships between prp(sc) stability and incubation time for united states scrapie isolates in a natural host system |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419241/ https://www.ncbi.nlm.nih.gov/pubmed/22916207 http://dx.doi.org/10.1371/journal.pone.0043060 |
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