Hofmeister effect in RT-QuIC seeding activity of Chronic Wasting Disease prions

Authors: HWANG, SOYOUN; BECKLEY, DANIELLE - ORISE FELLOW; ALEKSEEV, KONSTANTIN - ORISE FELLOW; Nicholson, Eric

Submitted to: Frontiers in Bioengineering and Biotechnology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/16/2021
Publication Date: 9/30/2021
Citation: Hwang, S., Beckley, D., Alekseev, K.P., Nicholson, E.M. 2021. Hofmeister effect in RT-QuIC seeding activity of Chronic Wasting Disease prions. Frontiers in Bioengineering and Biotechnology. 9. Article 709965. https://doi.org/10.3389/fbioe.2021.709965.
DOI: https://doi.org/10.3389/fbioe.2021.709965

Interpretive Summary: Chronic wasting disease (CWD) is a transmissibe spongiform encephalopathy (TSE) in free ranging and captive cervid species in North America, South Korea, Finland, Norway, and Sweden. The disease process occurs through the misfolding a of normally occuring protein. Case numbers are increasing at least in part due to the relative ease of animal to animal transmission in natural settings. Detection of the misfolded protein associated with the disease is the only known means by which a prion disease can be diagnosed. Typically this is only possible using tissues that are only available after death, such as brain. A recently developed approach for the detection of this misfolded protein uses a technique referred to as Real-time quaking induced conversion (RT-QuIC). RT-QuIC amplifies the amount of misfolded protein available for detection allowing for detection of smaller amounts of the prion protein that are present in other tissues, secretions, and excretions. In this work we extend and evaluate a method we previously developed to detection prions in fecal samples of white tailed deer infected with chronic wasting disease (CWD) well before the onset of clinical disease.

Technical Abstract: Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) that causes a fatal neurodegenerative disease in cervids. of free range and captive cervids which is a fatal neurodegenerative disease. Cases of CWD are rapidly increasing in North America among both wild and farmed cervid populations. Therefore, in order to manage the disease, it is imperative to devise a system that can detect CWD during the early phases of the disease. Real-time quaking-induced conversion (RT-QuIC) assays have been applied to detect infectious 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 that differing ionic environment can enhance or diminish the seeding activity. 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.