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Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep
The transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders characterised by the accumulation of a pathological form of a host protein known as prion protein (PrP). The validation of abnormal PrP detection techniques is fundamental to allow...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373927/ https://www.ncbi.nlm.nih.gov/pubmed/25807559 http://dx.doi.org/10.1371/journal.pone.0122785 |
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author | Chianini, Francesca Cosseddu, Gian Mario Steele, Philip Hamilton, Scott Hawthorn, Jeremy Síso, Sílvia Pang, Yvonne Finlayson, Jeanie Eaton, Samantha L. Reid, Hugh W. Dagleish, Mark P. Di Bari, Michele Angelo D’Agostino, Claudia Agrimi, Umberto Terry, Linda Nonno, Romolo |
author_facet | Chianini, Francesca Cosseddu, Gian Mario Steele, Philip Hamilton, Scott Hawthorn, Jeremy Síso, Sílvia Pang, Yvonne Finlayson, Jeanie Eaton, Samantha L. Reid, Hugh W. Dagleish, Mark P. Di Bari, Michele Angelo D’Agostino, Claudia Agrimi, Umberto Terry, Linda Nonno, Romolo |
author_sort | Chianini, Francesca |
collection | PubMed |
description | The transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders characterised by the accumulation of a pathological form of a host protein known as prion protein (PrP). The validation of abnormal PrP detection techniques is fundamental to allow the use of high-throughput laboratory based tests, avoiding the limitations of bioassays. We used scrapie, a prototype TSE, to examine the relationship between infectivity and laboratory based diagnostic tools. The data may help to optimise strategies to prevent exposure of humans to small ruminant TSE material via the food chain. Abnormal PrP distribution/accumulation was assessed by immunohistochemistry (IHC), Western blot (WB) and ELISA in samples from four animals. In addition, infectivity was detected using a sensitive bank vole bioassay with selected samples from two of the four sheep and protein misfolding cyclic amplification using bank vole brain as substrate (vPMCA) was also carried out in selected samples from one animal. Lymph nodes, oculomotor muscles, sciatic nerve and kidney were positive by IHC, WB and ELISA, although at levels 100–1000 fold lower than the brain, and contained detectable infectivity by bioassay. Tissues not infectious by bioassay were also negative by all laboratory tests including PMCA. Although discrepancies were observed in tissues with very low levels of abnormal PrP, there was an overall good correlation between IHC, WB, ELISA and bioassay results. Most importantly, there was a good correlation between the detection of abnormal PrP in tissues using laboratory tests and the levels of infectivity even when the titre was low. These findings provide useful information for risk modellers and represent a first step toward the validation of laboratory tests used to quantify prion infectivity, which would greatly aid TSE risk assessment policies. |
format | Online Article Text |
id | pubmed-4373927 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43739272015-03-27 Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep Chianini, Francesca Cosseddu, Gian Mario Steele, Philip Hamilton, Scott Hawthorn, Jeremy Síso, Sílvia Pang, Yvonne Finlayson, Jeanie Eaton, Samantha L. Reid, Hugh W. Dagleish, Mark P. Di Bari, Michele Angelo D’Agostino, Claudia Agrimi, Umberto Terry, Linda Nonno, Romolo PLoS One Research Article The transmissible spongiform encephalopathies (TSEs) or prion diseases are a group of fatal neurodegenerative disorders characterised by the accumulation of a pathological form of a host protein known as prion protein (PrP). The validation of abnormal PrP detection techniques is fundamental to allow the use of high-throughput laboratory based tests, avoiding the limitations of bioassays. We used scrapie, a prototype TSE, to examine the relationship between infectivity and laboratory based diagnostic tools. The data may help to optimise strategies to prevent exposure of humans to small ruminant TSE material via the food chain. Abnormal PrP distribution/accumulation was assessed by immunohistochemistry (IHC), Western blot (WB) and ELISA in samples from four animals. In addition, infectivity was detected using a sensitive bank vole bioassay with selected samples from two of the four sheep and protein misfolding cyclic amplification using bank vole brain as substrate (vPMCA) was also carried out in selected samples from one animal. Lymph nodes, oculomotor muscles, sciatic nerve and kidney were positive by IHC, WB and ELISA, although at levels 100–1000 fold lower than the brain, and contained detectable infectivity by bioassay. Tissues not infectious by bioassay were also negative by all laboratory tests including PMCA. Although discrepancies were observed in tissues with very low levels of abnormal PrP, there was an overall good correlation between IHC, WB, ELISA and bioassay results. Most importantly, there was a good correlation between the detection of abnormal PrP in tissues using laboratory tests and the levels of infectivity even when the titre was low. These findings provide useful information for risk modellers and represent a first step toward the validation of laboratory tests used to quantify prion infectivity, which would greatly aid TSE risk assessment policies. Public Library of Science 2015-03-25 /pmc/articles/PMC4373927/ /pubmed/25807559 http://dx.doi.org/10.1371/journal.pone.0122785 Text en © 2015 Chianini et al 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 Chianini, Francesca Cosseddu, Gian Mario Steele, Philip Hamilton, Scott Hawthorn, Jeremy Síso, Sílvia Pang, Yvonne Finlayson, Jeanie Eaton, Samantha L. Reid, Hugh W. Dagleish, Mark P. Di Bari, Michele Angelo D’Agostino, Claudia Agrimi, Umberto Terry, Linda Nonno, Romolo Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep |
title | Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep |
title_full | Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep |
title_fullStr | Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep |
title_full_unstemmed | Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep |
title_short | Correlation between Infectivity and Disease Associated Prion Protein in the Nervous System and Selected Edible Tissues of Naturally Affected Scrapie Sheep |
title_sort | correlation between infectivity and disease associated prion protein in the nervous system and selected edible tissues of naturally affected scrapie sheep |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373927/ https://www.ncbi.nlm.nih.gov/pubmed/25807559 http://dx.doi.org/10.1371/journal.pone.0122785 |
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