Relationships between PrPSc 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...

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Autores principales: Catherine E Vrentas, Justin J Greenlee, Trudy L Tatum, Eric M Nicholson
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Publicado: Public Library of Science (PLoS) 2012
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spelling oai:doaj.org-article:fd1c0a5342bb469db4c04cd6110afb0c2021-11-18T07:08:44ZRelationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system.1932-620310.1371/journal.pone.0043060https://doaj.org/article/fd1c0a5342bb469db4c04cd6110afb0c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22916207/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Transmissible 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.Catherine E VrentasJustin J GreenleeTrudy L TatumEric M NicholsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e43060 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Catherine E Vrentas
Justin J Greenlee
Trudy L Tatum
Eric M Nicholson
Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system.
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 article
author Catherine E Vrentas
Justin J Greenlee
Trudy L Tatum
Eric M Nicholson
author_facet Catherine E Vrentas
Justin J Greenlee
Trudy L Tatum
Eric M Nicholson
author_sort Catherine E Vrentas
title Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system.
title_short Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system.
title_full Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system.
title_fullStr Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system.
title_full_unstemmed Relationships between PrPSc stability and incubation time for United States scrapie isolates in a natural host system.
title_sort relationships between prpsc stability and incubation time for united states scrapie isolates in a natural host system.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/fd1c0a5342bb469db4c04cd6110afb0c
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