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Factors affecting the non-structural functions of Rubella virus capsid

  • Author / Creator
    Willows, Steven D
  • During infection, the host cell environment must be altered to accommodate viral replication. These alterations include hijacking cellular membranes as well as other components to form viral replication compartments and attenuating the host defenses to prevent virus detection and elimination. While DNA viruses can encode single purpose proteins dedicated for these functions, RNA viruses have a more limited coding capacity and instead utilize proteins with multiple functions. Rubella virus, a single-stranded, positive-sense RNA virus in the family Togaviridae, is one example. The capsid protein of this virus, which forms the protective protein shell around the genomic RNA in the virion, also fulfils several non-structural roles during infection. While previous studies have revealed several host proteins that are associated with these non-structural roles, more work is needed in order to fully understand how capsid alters the host cell environment. In this thesis, I investigated factors that affect the ability of capsid to inhibit apoptosis, a mechanism used to limit viral replication and eliminate infected cells within multicellular organisms. I found that phosphorylation and membrane association of capsid are important for its anti-apoptotic function, with both being necessary to prevent sequestration of capsid in RNA rich regions of the cell. Furthermore, I discovered that a canonical binding site for protein phosphatase 1 (PP1) is important for the anti-apoptotic function of capsid as well as its role in virion assembly. Finally, I showed that the capsid protein antagonizes innate immune signaling, a function that is dependent on its PP1-binding site.

  • Subjects / Keywords
  • Graduation date
    2015-11
  • Type of Item
    Thesis
  • Degree
    Doctor of Philosophy
  • DOI
    https://doi.org/10.7939/R3PK0767W
  • 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 Cell Biology
  • Supervisor / co-supervisor and their department(s)
    • Hobman, Tom (Cell Biology)
  • Examining committee members and their departments
    • Jean, François (Microbiology and Immunology)
    • Hobman, Tom (Cell Biology)
    • Goping, Ing Swie (Biochemistry)
    • Shmulevitz, Maya (Medical Microbiology and Immunology)
    • Simmen, Thomas (Cell Biology)