Adaptive selection of a prion strain conformer corresponding to established North American CWD during propagation of novel emergent Norwegian strains in mice expressing elk or deer prion protein

Simple item page

Simple item page

Full item details

creativework.keywords - en
Transmissible spongiform encephalopathies
Prions--Transmission
Chronic wasting disease
creativework.keywords - fr
Encéphalopathies spongiformes transmissibles
Prions (Virologie)--Transmission
Maladie du dépérissement chronique
dc.contributor.author
Bian, Jifeng
Kim, Sehun
Kane, Sarah J.
Crowell, Jenna
Sun, Julianna L.
Christiansen, Jeffery
Saijo, Eri
Moreno, Julie A.
DiLisio, James
Burnett, Emily
Pritzkow, Sandra
Gorski, Damian
Sots, Claudio
Kreeger, Terry J.
Balachandran, Aru
Mitchell, Gordon
Miller, Michael W.
Nonno, Romolo
Vikøren, Turid
Våge, Jørn
Madslien, Knut
Tran, Linh
Vuong, Tram Thu
Benestad, Sylvie L.
Telling, Glenn C.
dc.date.accepted
2021-06-24
dc.date.accessioned
2025-03-31T14:40:45Z
dc.date.available
2025-03-31T14:40:45Z
dc.date.issued
2021-07-26
dc.date.submitted
2021-03-15
dc.description.abstract - en
Prions are infectious proteins causing fatal, transmissible neurodegenerative diseases of animals and humans. Replication involves template-directed refolding of host encoded prion protein, PrPC, by its infectious conformation, PrPSc. Following its discovery in captive Colorado deer in 1967, uncontrollable contagious transmission of chronic wasting disease (CWD) led to an expanded geographic range in increasing numbers of free-ranging and captive North American (NA) cervids. Some five decades later, detection of PrPSc in free-ranging Norwegian (NO) reindeer and moose marked the first indication of CWD in Europe. To assess the properties of these emergent NO prions and compare them with NA CWD we used transgenic (Tg) and gene targeted (Gt) mice expressing PrP with glutamine (Q) or glutamate (E) at residue 226, a variation in wild type cervid PrP which influences prion strain selection in NA deer and elk. Transmissions of NO moose and reindeer prions to Tg and Gt mice recapitulated the characteristic features of CWD in natural hosts, revealing novel prion strains with disease kinetics, neuropathological profiles, and capacities to infect lymphoid tissues and cultured cells that were distinct from those causing NA CWD. In support of strain variation, PrPSc conformers comprising emergent NO moose and reindeer CWD were subject to selective effects imposed by variation at residue 226 that were different from those controlling established NA CWD. Transmission of particular NO moose CWD prions in mice expressing E at 226 resulted in selection of a kinetically optimized conformer, subsequent transmission of which revealed properties consistent with NA CWD. These findings illustrate the potential for adaptive selection of strain conformers with improved fitness during propagation of unstable NO prions. Their potential for contagious transmission has implications for risk analyses and management of emergent European CWD. Finally, we found that Gt mice expressing physiologically controlled PrP levels recapitulated the lymphotropic properties of naturally occurring CWD strains resulting in improved susceptibilities to emergent NO reindeer prions compared with over-expressing Tg counterparts. These findings underscore the refined advantages of Gt models for exploring the mechanisms and impacts of strain selection in peripheral compartments during natural prion transmission.
dc.identifier.citation
Bian, J., Kim, S., Kane, S. J., Crowell, J., Sun, J. L., Christiansen, J., Saijo, E., Moreno, J. A., DiLisio, J., Burnett, E., Pritzkow, S., Gorski, D., Soto, C., Kreeger, T. J., Balachandran, A., Mitchell, G., Miller, M. W., Nonno, R., Vikørn, T., Våge, J., Madslien, K., Tran, L., Vuong, T. T., Benestad, S. L., & Telling, G. C. (2021). Adaptive selection of a prion strain conformer corresponding to established North American CWD during propagation of novel emergent Norwegian strains in mice expressing elk or deer prion protein. PLoS Pathogens 17(7), Article e1009748. https://doi.org/10.1371/journal.ppat.1009748
dc.identifier.doi
https://doi.org/10.1371/journal.ppat.1009748
dc.identifier.uri
https://open-science.canada.ca/handle/123456789/3558
dc.language.iso
en
dc.publisher - en
Public Library of Science
dc.rights - en
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights - fr
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.rights.uri - en
https://creativecommons.org/licenses/by/4.0/
dc.rights.uri - fr
https://creativecommons.org/licenses/by/4.0/deed.fr
dc.subject - en
Infectious diseases
dc.subject - fr
Maladie infectieuse
dc.subject.en - en
Infectious diseases
dc.subject.fr - fr
Maladie infectieuse
dc.title - en
Adaptive selection of a prion strain conformer corresponding to established North American CWD during propagation of novel emergent Norwegian strains in mice expressing elk or deer prion protein
dc.type - en
Article
dc.type - fr
Article
local.acceptedmanuscript.articlenum
e1009748
local.article.journalissue
7
local.article.journaltitle - en
PLOS Pathogens
local.article.journalvolume
17
local.pagination
1-33
local.peerreview - en
Yes
local.peerreview - fr
Oui
local.requestdoi
No
Download(s)

Original bundle

Now showing 1 - 1 of 1

Thumbnail image

Name: AdaptiveSelectionOfAPrionStrainConformerCorrespondingToEstablishedNorthAmericanCWDDuringPropagationOfNovelEmergentNorwegianStrainsInMice_2021.pdf

Size: 4.82 MB

Format: PDF

Download file

Collection(s)

Page details

Date modified: