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Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that causes a fatal neurodegenerative disease in cervids. Cases of CWD are rapidly increasing in North America among wild and farmed cervid populations, and potential for zoonotic transmission is not yet determined. The...

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Autores principales: Hwang, Soyoun, Beckley, Danielle, Alekseev, Konstantin P., Nicholson, Eric M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515057/
https://www.ncbi.nlm.nih.gov/pubmed/34660549
http://dx.doi.org/10.3389/fbioe.2021.709965
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author Hwang, Soyoun
Beckley, Danielle
Alekseev, Konstantin P.
Nicholson, Eric M.
author_facet Hwang, Soyoun
Beckley, Danielle
Alekseev, Konstantin P.
Nicholson, Eric M.
author_sort Hwang, Soyoun
collection PubMed
description Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that causes a fatal neurodegenerative disease in cervids. Cases of CWD are rapidly increasing in North America among wild and farmed cervid populations, and potential for zoonotic transmission is not yet determined. Therefore, in order to manage the disease, it is imperative to devise a system that can detect CWD during its early phases to prevent spread to new captive herds through introduction of CWD-affected animals into otherwise CWD-free herds. Real-time quaking–induced conversion (RT-QuIC) assays have been applied to detect the presence of disease-associated prions from various samples in both animals and humans. In this study, we have tested the use of five Hofmeister anions that range from weakly hydrating to strongly hydrating: Na(3)citrate, Na(2)SO(4), NaCl, NaI, and NaClO(4) in RT-QuIC reactions for CWD seeding activity using different recombinant prion proteins as substrates. This work shows how the ionic environment of the RT-QuIC reaction can enhance or diminish the seeding activity. The use of Na(2)SO(4) or NaI as the sodium salt for RT-QuIC using bank vole recombinant prion substrate for the detection of CWD using brain samples reduces the lag time to detect with reasonable specificity. For detection of the CWD in fecal samples, only NaI showed comparable reduction in lag time relative to NaCl but required reduced temperature to alleviate spontaneous fibril formation in negative control samples. Selection of the proper ion environment and recombinant prion protein substrate will make RT-QuIC a powerful diagnostic tool for early detection of CWD prions, further supporting CWD surveillance in wild and captive cervids.
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spelling pubmed-85150572021-10-15 Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions Hwang, Soyoun Beckley, Danielle Alekseev, Konstantin P. Nicholson, Eric M. Front Bioeng Biotechnol Bioengineering and Biotechnology Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that causes a fatal neurodegenerative disease in cervids. Cases of CWD are rapidly increasing in North America among wild and farmed cervid populations, and potential for zoonotic transmission is not yet determined. Therefore, in order to manage the disease, it is imperative to devise a system that can detect CWD during its early phases to prevent spread to new captive herds through introduction of CWD-affected animals into otherwise CWD-free herds. Real-time quaking–induced conversion (RT-QuIC) assays have been applied to detect the presence of disease-associated prions from various samples in both animals and humans. In this study, we have tested the use of five Hofmeister anions that range from weakly hydrating to strongly hydrating: Na(3)citrate, Na(2)SO(4), NaCl, NaI, and NaClO(4) in RT-QuIC reactions for CWD seeding activity using different recombinant prion proteins as substrates. This work shows how the ionic environment of the RT-QuIC reaction can enhance or diminish the seeding activity. The use of Na(2)SO(4) or NaI as the sodium salt for RT-QuIC using bank vole recombinant prion substrate for the detection of CWD using brain samples reduces the lag time to detect with reasonable specificity. For detection of the CWD in fecal samples, only NaI showed comparable reduction in lag time relative to NaCl but required reduced temperature to alleviate spontaneous fibril formation in negative control samples. Selection of the proper ion environment and recombinant prion protein substrate will make RT-QuIC a powerful diagnostic tool for early detection of CWD prions, further supporting CWD surveillance in wild and captive cervids. Frontiers Media S.A. 2021-09-30 /pmc/articles/PMC8515057/ /pubmed/34660549 http://dx.doi.org/10.3389/fbioe.2021.709965 Text en Copyright © 2021 Hwang, Beckley, Alekseev and Nicholson. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Hwang, Soyoun
Beckley, Danielle
Alekseev, Konstantin P.
Nicholson, Eric M.
Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions
title Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions
title_full Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions
title_fullStr Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions
title_full_unstemmed Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions
title_short Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions
title_sort hofmeister effect in rt-quic seeding activity of chronic wasting disease prions
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515057/
https://www.ncbi.nlm.nih.gov/pubmed/34660549
http://dx.doi.org/10.3389/fbioe.2021.709965
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