|dc.contributor.author||Henriquez, Rodney Fabian||-|
|dc.description.abstract||Varicella Zoster Virus (VZV) is a species specific alpha human herpes virus that causes both Varicella (chickenpox) and Herpes Zoster (shingles) in human hosts. It has been hypothesized that host dendritic cells (DC) play a pivotal role in the pathogenesis of VZV during the early stages of infection. DC have previously been shown to be permissive to VZV infection and capable of transmitting the virus to human T lymphocytes. VZV has also been shown to employ a variety of mechanisms to evade detection and clearance by the host immune system.
The primary aim of this study was to identify the underlying mechanisms beneath the virus induced modulation of mature DC effector functions. Observation of the kinetics of VZV mediated downregulation of the DC immune molecules CD80, CD83 and CD86 in addition to the block of Late viral gene products demonstrated that de novo viral protein synthesis of the immediate early or early class, were required to mediate modulation of CD80, CD83 and CD86. Blocking of the host cell proteasome had a restorative effect on the cell surface expression of CD86 in VZV infected mature DC.
Analysis of a panel of gene transcripts involved in the effector functions of human DC in VZV infected mature DC identified significant changes in cytokine and chemokine expression (IL-8 & MIF), cytokine and chemokine receptor expression (CXCR-4 & FLT-3) and other functionally important immune molecule expression (CD44, CD80 & HLA-DPA1). Some of these changes suggest that VZV actively induces changes to host DC transcripts in order to maintain an immature state and thus negate the effector function of mature DC.
The migratory capabilities of VZV infected mature DC was shown to be compromised. Furthermore, it was shown that the few still capable of migration had significantly reduced levels of cell surface CD83. Taken together, the results presented identify a wide range of mechanisms by which VZV modulates mature DC effector functions.||en_AU|
|dc.publisher||University of Sydney||en_AU|
|dc.publisher||School of Medicine||en_AU|
|dc.publisher||Centre for Virus Research, Westmead Millennium Institute||en_AU|
|dc.rights||The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.||en_AU|
|dc.title||Varicella Zoster Virus infection of human matured monocyte derived dendritic cells & its impact on their effector functions||en_AU|
|dc.type.pubtype||Master of Philosophy M.Phil||en_AU|
|dc.description.disclaimer||Access is restricted to staff and students of the University of Sydney . UniKey credentials are required. Non university access may be obtained by visiting the University of Sydney Library.||en_AU|
|Appears in Collections:||Sydney Digital Theses (University of Sydney Access only)|