KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    •   KU ScholarWorks
    • Dissertations and Theses
    • Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Interplay Between Viral and Cellular Factors Determines the Fate of Herpes Simplex Virus type I Infection

    Thumbnail
    View/Open
    MabroukMostafa_ku_0099D_13292_DATA_1.pdf (4.838Mb)
    Issue Date
    2014-05-31
    Author
    Mabrouk-Mostafa, Heba
    Publisher
    University of Kansas
    Format
    187 pages
    Type
    Dissertation
    Degree Level
    Ph.D.
    Discipline
    Molecular Biosciences
    Rights
    This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author.
    Metadata
    Show full item record
    Abstract
    The herpes simplex virus type I (HSV-1) is a major human pathogen that infects the majority of the world's population. The life cycle of HSV-1 is controlled by interactions with its hosts. Understanding virus-host interactions will be necessary for developing new therapeutic and preventive strategies against HSV-1, especially in immuno-compromised patients and neonates. An interesting aspect of HSV-1 is how it switches from a productive (lytic) replication cycle to a lifelong latent infection in the sensory neurons; the molecular events involved in this switch are not clearly understood. Consequently, the major goal of this thesis is to examine the role and interactions of viral and cellular proteins in determining the outcome of viral infection. In this thesis, I studied two viral regulatory immediate early proteins (IE), namely infected cell protein 0 (ICP0) and infected cell protein 22 (ICP22). Both proteins are required for efficient viral replication in vivo. Specifically, I characterized in cell culture and in mice how ICP0's functions are regulated via phosphorylation, and I distinguished the functions between ICP22 versus its N-terminally truncated form, US1.5. In the latter experiments, we also identified a novel role for ICP22 in counteracting the type I interferon (IFN) response. Furthermore, I characterized the viral mutant, KOS-NA that contains novel mutation/s within the UL39 gene, which encodes for the large subunit of ribonucleotide reducatese enzyme (ICP6). These mutations in KOS-NA resulted in ICP6 amino acid substitutions that reduced its protein levels, and attenuated viral pathogenesis in vivo, making KOS-NA a potential therapeutic vector in treating HSV-1 diseases. Lastly, I discovered a new relation between the cellular kinase CDK-5, its activating partner p35, and HSV-1 acute infection of neurons. Overall, the data presented in this thesis indicates that multiple viral encoded factors, phosphorylation, cellular factors, and their interactions with one another affect the HSV-1 life cycle.
    URI
    http://hdl.handle.net/1808/14534
    Collections
    • Molecular Biosciences Dissertations and Theses [273]
    • Dissertations [4473]

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps