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Permanent link (DOI): https://doi.org/10.7939/R3JQ0T68J

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Cervid Prion Protein Polymorphisms Modulate the Diversity of Chronic Wasting Disease Prion Strains Open Access

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Other title
Subject/Keyword
Cervid
Polymorphisms
Strains
Prion
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Duque Velasquez, Juan C
Supervisor and department
Judd Aiken
Examining committee member and department
McKenzie, Debbie (Biological Sciences)
Uwiera, Richard (Agricultural, Food and Nutritional Science)
Bartz, Jason (Medical Microbiology and Immunology, Creighton University, Nebraska, US)
Sim, Valerie (Medicine)
Department
Department of Agricultural, Food, and Nutritional Science
Specialization
Animal Science
Date accepted
2017-03-30T10:23:53Z
Graduation date
2017-06:Spring 2017
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Chronic wasting disease (CWD) is a contagious prion disease spreading and emerging in wild and captive Cervidae species worldwide. Prion diseases are fatal neurodegenerative disorders occurring in various mammalian species including deer, elk, sheep, cattle and humans. Central to prion pathogenesis is the PRNP gene, which encodes the cellular prion protein (PrPC), a membrane glycoprotein that is primarily expressed in the brain. The pathogenesis of prion diseases involves the misfolding of PrPC into self-replicating, strain-encoding PrPSc (PrPCWD for cervid infections) conformers termed “prions”. Single PrPC amino acid polymorphisms can influence aspects of the disease, including susceptibility, clinical presentation and pathological phenotypes. In cervids, transmission of CWD occurs within and between species expressing PRNP allelic variants. A potential consequence of prion transmission between hosts with different PrPC primary structures is the emergence of CWD strains with novel transmission properties. These studies characterize the biological effects of CWD propagation in deer expressing different PrPC molecules: I) PrPC amino acid polymorphisms H95 and S96 subjected CWD prions to selective propagation barriers that modified the spectra of PrPCWD conformers. II) Transmission of PrPCWD conformational variants resulted in the emergence of a novel CWD strain that was selected in concert with the host recipient PrPC. III) CWD transmission between deer expressing different PrPC primary structures expanded the host range of CWD. These results suggest that circulating CWD strains would diversify as transmission between different cervid PRNP genotypes occurs. Understanding the effects of PrPC polymorphisms on the properties of CWD strains could help identify key events in their replication and spread.
Language
English
DOI
doi:10.7939/R3JQ0T68J
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
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