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Determining the functional impact of KSHV infection of endothelial cells

Jeffery, Hannah Claire (2012)
Ph.D. thesis, University of Birmingham.

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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-\(\alpha\)4 chain. No effect on deposition of either fibronectin or collagen IV was found. An increase in cell-surface expression of the lamininbinding integrin-\(\alpha\)6 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.

Type of Work:Ph.D. thesis.
Supervisor(s):Blackbourn, David J. and Nash, G. B. (Gerard B.)
School/Faculty:Schools (1998 to 2008) > School of Medicine
Department:School of Cancer Studies
Subjects:R Medicine (General)
RK Dentistry
Institution:University of Birmingham
ID Code:3676
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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