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

  • Author / Creator
    Duque Velasquez, Juan C
  • 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.

  • Subjects / Keywords
  • Graduation date
    2017-06
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3JQ0T68J
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. 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.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Doctoral
  • Department
    • Department of Agricultural, Food, and Nutritional Science
  • Specialization
    • Animal Science
  • Supervisor / co-supervisor and their department(s)
    • Judd Aiken
  • Examining committee members and their departments
    • McKenzie, Debbie (Biological Sciences)
    • Sim, Valerie (Medicine)
    • Bartz, Jason (Medical Microbiology and Immunology, Creighton University, Nebraska, US)
    • Uwiera, Richard (Agricultural, Food and Nutritional Science)