Extraneural infection route restricts prion conformational variability and attenuates the impact of quaternary structure on infectivity
Extraneural infection route restricts prion conformational variability and attenuates the impact of quaternary structure on infectivity
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- creativework.keywords - en
- Bovine spongiform encephalopathies
- Chronic wasting disease
- Cervidae--Diseases
- Communicable diseases--Transmission
- creativework.keywords - fr
- Encéphalopathies spongiformes bovines
- Maladie du dépérissement chronique
- Cervidés--Maladies
- Maladies infectieuses--Transmission
- dc.contributor.author
- Chang, Sheng Chun
- Arifin, Maria Immaculata
- Tahir, Waqas
- McDonald, Keegan John
- Zeng, Doris
- Schatzl, Hermann M.
- Hannaoui, Samia
- Gilch, Sabine
- dc.date.accepted
- 2024-06-25
- dc.date.accessioned
- 2025-04-08T18:11:42Z
- dc.date.available
- 2025-04-08T18:11:42Z
- dc.date.issued
- 2024-07-08
- dc.date.submitted
- 2024-03-26
- dc.description.abstract - en
- Prions can exist as different strains that consist of conformational variants of the misfolded, pathogenic prion protein isoform PrPSc. Defined by stably transmissible biological and biochemical properties, strains have been identified in a spectrum of prion diseases, including chronic wasting disease (CWD) of wild and farmed cervids. CWD is highly contagious and spreads via direct and indirect transmission involving extraneural sites of infection, peripheral replication and neuroinvasion of prions. Here, we investigated the impact of infection route on CWD prion conformational selection and propagation. We used gene-targeted mouse models expressing deer PrP for intracerebral or intraperitoneal inoculation with fractionated or unfractionated brain homogenates from white-tailed deer, harboring CWD strains Wisc-1 or 116AG. Upon intracerebral inoculation, Wisc-1 and 116AG-inoculated mice differed in conformational stability of PrPSc. In brains of mice infected intraperitoneally with either inoculum, PrPSc propagated with identical conformational stability and fewer PrPSc deposits in most brain regions than intracerebrally inoculated animals. For either inoculum, PrPSc conformational stability in brain and spinal cord was similar upon intracerebral infection but significantly higher in spinal cords of intraperitoneally infected animals. Inoculation with fractionated brain homogenates resulted in lower variance of survival times upon intraperitoneal compared to intracerebral infection. In summary, we demonstrate that extraneural infection mitigates the impact of PrPSc quaternary structure on infection and reduces conformational variability of PrPSc propagated in the brain. These findings provide new insights into the evolution of stable CWD strains in natural, extraneural transmissions.
- dc.identifier.citation
- Chang, S. C., Arifin, M. I., Tahir, W., McDonald, K. J., Zeng, D., Schatzl, H. M., Hannaoui, S., & Gilch, S. (2024). Extraneural infection route restricts prion conformational variability and attenuates the impact of quaternary structure on infectivity. PLoS Pathogens, 20(7), Article e1012370. https://doi.org/10.1371/journal.ppat.1012370
- dc.identifier.doi
- https://doi.org/10.1371/journal.ppat.1012370
- dc.identifier.issn
- 1553-7374
- dc.identifier.uri
- https://open-science.canada.ca/handle/123456789/3593
- dc.language.iso
- en
- dc.publisher - en
- Public Library of Science
- dc.publisher - fr
- 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
- Animal diseases
- dc.subject - fr
- Maladie animale
- dc.subject.en - en
- Animal diseases
- dc.subject.fr - fr
- Maladie animale
- dc.title - en
- Extraneural infection route restricts prion conformational variability and attenuates the impact of quaternary structure on infectivity
- dc.type - en
- Article
- dc.type - fr
- Article
- local.acceptedmanuscript.articlenum
- e1012370
- local.article.journalissue
- 7
- local.article.journaltitle - en
- PLoS Pathogens
- local.article.journalvolume
- 20
- local.pagination
- 1-19
- local.peerreview - en
- Yes
- local.peerreview - fr
- Oui
- local.requestdoi
- No
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