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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doaj-fddb0ee4ca7e4fa99171c6448024e6b92021-09-30T08:42:06ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852021-09-01910.3389/fbioe.2021.709965709965Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease PrionsSoyoun Hwang0Danielle Beckley1Danielle Beckley2Konstantin P. Alekseev3Konstantin P. Alekseev4Konstantin P. Alekseev5Eric M. Nicholson6United States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United StatesUnited States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United StatesU.S. Department of Energy, Oak Ridge Institute for Science and Education, Oak Ridge, TN, United StatesUnited States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United StatesU.S. Department of Energy, Oak Ridge Institute for Science and Education, Oak Ridge, TN, United StatesN. F. Gamaleya National Research Center for Epidemiology and Microbiology, Moscow, RussiaUnited States Department of Agriculture, Agricultural Research Service, National Animal Disease Center, Virus and Prion Research Unit, Ames, IA, United StatesChronic 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: Na3citrate, Na2SO4, NaCl, NaI, and NaClO4 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 Na2SO4 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.https://www.frontiersin.org/articles/10.3389/fbioe.2021.709965/fullHofmeister seriessalt ionsprion diseaseschronic wasting disease (CWD)RT-QuICdiagnostics |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Soyoun Hwang Danielle Beckley Danielle Beckley Konstantin P. Alekseev Konstantin P. Alekseev Konstantin P. Alekseev Eric M. Nicholson |
spellingShingle |
Soyoun Hwang Danielle Beckley Danielle Beckley Konstantin P. Alekseev Konstantin P. Alekseev Konstantin P. Alekseev Eric M. Nicholson Hofmeister Effect in RT-QuIC Seeding Activity of Chronic Wasting Disease Prions Frontiers in Bioengineering and Biotechnology Hofmeister series salt ions prion diseases chronic wasting disease (CWD) RT-QuIC diagnostics |
author_facet |
Soyoun Hwang Danielle Beckley Danielle Beckley Konstantin P. Alekseev Konstantin P. Alekseev Konstantin P. Alekseev Eric M. Nicholson |
author_sort |
Soyoun Hwang |
title |
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_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_sort |
hofmeister effect in rt-quic seeding activity of chronic wasting disease prions |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Bioengineering and Biotechnology |
issn |
2296-4185 |
publishDate |
2021-09-01 |
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: Na3citrate, Na2SO4, NaCl, NaI, and NaClO4 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 Na2SO4 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. |
topic |
Hofmeister series salt ions prion diseases chronic wasting disease (CWD) RT-QuIC diagnostics |
url |
https://www.frontiersin.org/articles/10.3389/fbioe.2021.709965/full |
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