Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.558926
Title: Determining the functional impact of kshv infection of endothelial cells
Author: Jeffery, Hannah Claire
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2012
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Abstract:
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the aetiologic agent of Kaposi’s sarcoma (KS), a malignancy characterised by spindle-shaped tumour cells with an endothelial phenotype that line primitive vascular structures. This thesis examines the concept that KSHV infection of primary endothelial cells alters their migration, supporting development of the extensive aberrant angiogenesis seen in KS.Primary human umbilical vein endothelial cells were infected with KSHV and their migration examined at time points between one and ten days post-inoculation. Infected cells transmigrated preferentially across porous filters compared to untreated or non-infected cells, and wounds in inoculated monolayers closed more rapidly compared to untreated cultures. Several cellular properties which might regulate cell migration rates were altered by KSHV inoculation. The virus modulated the laminin profile of the sub-endothelial matrix by reducing laminin-P1 deposition but increasing that of the laminin-a4 chain. No effect on deposition of either fibronectin or collagen IV was found. An increase in cell-surface expression of the lamininbinding integrin-a6 subunit was also detected with infection. Furthermore, KSHV infection partitioned actin stress fibres to the cell cortex and reduced the size and number of focal adhesions per cell. These results support a pro-migratory, pro-angiogenic effect of KSHV on endothelial cells that might be targeted to treat KS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.558926  DOI: Not available
Keywords: R Medicine (General) ; RK Dentistry
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