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dc.contributor.authorKennedy, Jarrod John
dc.date.accessioned2019-05-31T07:24:26Z
dc.date.available2019-05-31T07:24:26Z
dc.date.issued2018-12-31
dc.identifier.urihttp://hdl.handle.net/2123/20485
dc.description.abstractHuman herpesviruses are ubiquitous in almost all communities and species. Varicella Zoster Virus (VZV), an alphaherpesvirus, is the causative agent of chickenpox and shingles. VZV influences the immune system by evading immune recognition and subverting the immune response. This is predicated upon the susceptibility of immune cells to VZV infection, which also aids in the dissemination of VZV throughout the host. VZV infection of the immune cells is understudied and has likely limited our understanding of how VZV modulates the immune system. Human monocytes and macrophages are integral to recognition and resolution of viral infection. There is little consensus regarding the susceptibility of these cells to VZV infection. This study is the first to comprehensively identify the productive VZV infection of human monocytes and macrophages. Electron microscopy demonstrated the presence of virus in the nuclei and along the cell-surface of VZV infected monocytes. VZV infected monocytes transmitted VZV to permissive cells, suggesting they may be a source for viral dissemination in vivo. VZV infected monocytes limited the release of inflammatory cytokines and both VZV infected monocytes and macrophages demonstrated impaired endocytosis. Flow cytometry revealed significant modulation of the immune phenotype of infected monocytes and macrophages, including downregulation of molecules essential in differentiation and microbial ligand recognition. This suggests VZV impacts on microbial recognition and antigen presentation pathways. Monocyte viability was diminished during infection and monocytes were unable to generate viable macrophages. Overall, this study clearly demonstrates the susceptibility and modulation of an abundant and dynamic subset of innate immune cells to VZV infection, and provides multiple novel strategies through which VZV is able to control the immune system.en_AU
dc.publisherUniversity of Sydneyen_AU
dc.publisherFaculty of Medicine and Healthen_AU
dc.publisherInfectious Diseases and Immunologyen_AU
dc.rightsThe 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.subjectimmunologyen_AU
dc.subjectvirologyen_AU
dc.subjectinfectious diseasesen_AU
dc.subjectchicken poxen_AU
dc.subjectvaricellaen_AU
dc.subjectherpes virusen_AU
dc.titleInfection and Functional Modulation of Monocytes and Macrophages by Varicella Zoster Virusen_AU
dc.typePhD Doctorateen_AU
dc.type.pubtypeDoctor of Philosophy Ph.D.en_AU


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