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    Characterization of host-pathogen interactions in two model pathogens: Francisella tularensis and simian virus SV40

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    Author
    Smith, Lisa K.
    Chair
    Hueffer, Karsten
    Khun, Thomas
    Runstadler, Jonathan
    Metadata
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    URI
    http://hdl.handle.net/11122/4926
    Abstract
    We sought to elucidate the molecular mechanisms of host-pathogen interaction. The bacterium Francisella tularensis and simian virus SV40 represent two ideal model systems. Francisella tularensis is a facultative intracellular bacterium known to dampen the host immune response to infection. The Francisella pathogenicity island (FPI) encodes a cluster of 19 genes essential for full virulence and the observed change in immune response. We investigated the role of two FPI encoded proteins, PdpC and PdpD, on immune response. While both proteins affect a change, the effect of PdpD is more pronounced, and appears to play a role in modulation of host immune responses. SV40 is a DNA polyoma virus that targets GM1 receptors for entry into cells. The GM I receptor is localized to cholesterol-rich membrane microdomains, termed lipid rafts. Disruption of lipid rafts using the cholesterol chelator methyl-P-cyclodextrin prevents SV40 entry into cells. We investigated whether natural product alternatives would similarly disrupt lipid raft integrity and prevent viral entry. The triterpenoid ursolic acid, present in many plants, has been shown to possess antimicrobial properties and was used to treat cells prior to infection with SV40. We found ursolic acid to have no effect on the viral infectivity of SV40.
    Description
    Thesis (M.S.) University of Alaska Fairbanks, 2012
    Date
    2012-05
    Type
    Thesis
    Collections
    Chemistry and Biochemistry

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