Application of PMCA to understand CWD prion strains, species barrier and zoonotic potential

Authors: PRITZKOW, S - University Of Texas Medical Branch; GORSKI, DAMIAN - University Of Texas Medical Branch; RAMIREZ, FRANK - University Of Texas Medical Branch; WANG, FEI - University Of Texas Medical Branch; TELLING, GLENN - Colorado State University; Greenlee, Justin; BENESTAD, SYLVIE - Norwegian Veterinary Institute; SOTO, CLAUDIO - University Of Texas Medical Branch

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 6/22/2022
Publication Date: 9/11/2022
Citation: Pritzkow, S., Gorski, D., Ramirez, F., Wang, F., Telling, G.C., Greenlee, J.J., Benestad, S.L., Soto, C. 2022. Application of PMCA to understand CWD prion strains, species barrier and zoonotic potential. Prion 2022 Conference abstracts: pushing the boundaries. 16(1):209. https://doi.org/10.1080/19336896.2022.2091286.
DOI: https://doi.org/10.1080/19336896.2022.2091286

Interpretive Summary:

Technical Abstract: Chronic wasting disease (CWD) is a prion disease affecting various species of cervids that continue to spread uncontrollably across North America and has recently been detected in Northern Europe (Norway, Sweden and Finland). The mechanisms responsible for the individual-to-individual CWD transmission under natural conditions are for the most part unknown. The risk of transmission of CWD to other animal species or to humans is also unknown and remain a dangerous enigma. The main goal of this study was to investigate the potential of CWD prions to infect various species of animals (including sheep, cattle, pig, hamster and mice) and also humans, using as a proxy the ability of prions to convert the normal prion protein from distinct species in a PMCA reaction. We also studied whether in vivo passage of CWD through intermediate species may change the zoonotic potential of CWD prions. For these studies, we used brain material from CWD-infected white-tailed deer (Odocoileus virginianus), elk (Cervus canadensis), and mule deer (Odocoileus hemionus) were selected as species native to North America. We also used CWD-infected Moose (Alces alces), reindeer (Rangifer tarandus) and red deer (Cervus elaphus) as Norwegian cervids. We also used brains from cattle, sheep and pigs experimentally infected by CWD. To study interspecies-transmission and zoonotic potential, samples were tested in PMCA for the conversion of PrPC into PrPSc using different mixtures of inoculum and host species. Based on these analyses we estimated the spillover and zoonotic potential for different CWD isolates. We define and quantify spillover and zoonotic potential indices as the efficiency by which CWD prions sustain prion generation in vitro at expenses of normal prion proteins from various mammals and human, respectively. Our results show that prions from some cervid species, especially those found in Northern Europe, have a higher potential to transmit disease characteristics to other animals. Conversely, CWD infected cervids originated in North America appear to have a greater potential to generate human prions. We also found that in vivo transmission of CWD to cattle, but not to sheep or pigs substantially increase the ability of these prions to convert human PrPC by PMCA. Our findings support the existence of different CWD prion strains with distinct spillover and zoonotic potentials. We also conclude that transmission of CWD to other animal species may increase the risk for CWD transmission to humans. Our studies may provide a tool to predict the array of animal species that a given CWD prion could affect and may contribute to understand the risk of CWD for human health.