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Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads
Prions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low; therefore, direct diagnostic tests on such...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742390/ https://www.ncbi.nlm.nih.gov/pubmed/31513666 http://dx.doi.org/10.1371/journal.pone.0216013 |
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author | Hornemann, Simone Schwarz, Petra Rushing, Elisabeth J. Connolly, Michael D. Zuckermann, Ronald N. Yam, Alice Y. Aguzzi, Adriano |
author_facet | Hornemann, Simone Schwarz, Petra Rushing, Elisabeth J. Connolly, Michael D. Zuckermann, Ronald N. Yam, Alice Y. Aguzzi, Adriano |
author_sort | Hornemann, Simone |
collection | PubMed |
description | Prions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low; therefore, direct diagnostic tests on such specimens often yield false-negative results. Quantitative preanalytical prion enrichment may significantly improve the sensitivity of prion assays by concentrating trace amounts of prions from large volumes of body fluids. Here, we show that beads conjugated to positively charged peptoids not only captured PrP aggregates from plasma of prion-infected hamsters, but also adsorbed prion infectivity in both the symptomatic and preclinical stages of the disease. Bead absorbed prion infectivity efficiently transmitted disease to transgenic indicator mice. We found that the readout of the peptoid-based misfolded protein assay (MPA) correlates closely with prion infectivity in vivo, thereby validating the MPA as a simple, quantitative, and sensitive surrogate indicator of the presence of prions. The reliable and sensitive detection of prions in plasma will enable a wide variety of applications in basic prion research and diagnostics. |
format | Online Article Text |
id | pubmed-6742390 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-67423902019-09-20 Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads Hornemann, Simone Schwarz, Petra Rushing, Elisabeth J. Connolly, Michael D. Zuckermann, Ronald N. Yam, Alice Y. Aguzzi, Adriano PLoS One Research Article Prions cause transmissible infectious diseases in humans and animals and have been found to be transmissible by blood transfusion even in the presymptomatic stage. However, the concentration of prions in body fluids such as blood and urine is extremely low; therefore, direct diagnostic tests on such specimens often yield false-negative results. Quantitative preanalytical prion enrichment may significantly improve the sensitivity of prion assays by concentrating trace amounts of prions from large volumes of body fluids. Here, we show that beads conjugated to positively charged peptoids not only captured PrP aggregates from plasma of prion-infected hamsters, but also adsorbed prion infectivity in both the symptomatic and preclinical stages of the disease. Bead absorbed prion infectivity efficiently transmitted disease to transgenic indicator mice. We found that the readout of the peptoid-based misfolded protein assay (MPA) correlates closely with prion infectivity in vivo, thereby validating the MPA as a simple, quantitative, and sensitive surrogate indicator of the presence of prions. The reliable and sensitive detection of prions in plasma will enable a wide variety of applications in basic prion research and diagnostics. Public Library of Science 2019-09-12 /pmc/articles/PMC6742390/ /pubmed/31513666 http://dx.doi.org/10.1371/journal.pone.0216013 Text en https://creativecommons.org/publicdomain/zero/1.0/ 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. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Hornemann, Simone Schwarz, Petra Rushing, Elisabeth J. Connolly, Michael D. Zuckermann, Ronald N. Yam, Alice Y. Aguzzi, Adriano Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads |
title | Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads |
title_full | Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads |
title_fullStr | Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads |
title_full_unstemmed | Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads |
title_short | Enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads |
title_sort | enhanced detection of prion infectivity from blood by preanalytical enrichment with peptoid-conjugated beads |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742390/ https://www.ncbi.nlm.nih.gov/pubmed/31513666 http://dx.doi.org/10.1371/journal.pone.0216013 |
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