Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.652459
Title: Investigation of the mechanism of translation and contribution to pathogenesis of Kaposi's sarcoma associated herpesvirus FLICE inhibitory protein
Author: Hindley, C. E.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2005
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Abstract:
In this thesis the contribution of vFLIP toward viral pathogenesis has been investigated through the construction and use of recombinant murine gammaherpesviruses (MHV-76). KSHV vFLIP under the control of either the Cytomegalovirus immediate early (CMV-IE) or the murine phosphoglycerol kinase (PGK) promoter, together with enhanced green fluorescent protein (EGFP) and a hygromycin resistance marker, has been inserted into the left-hand end of the MHV-76 genome to produce recombinant viruses that have been used for in vivo and in vitro studies. All recombinant viruses display similar in vitro growth kinetics to wild-type MHV-76 during infection of BHK cells. Intranasal infection of Balb/c mice with CMV vFLIP viruses resulted in a 2 fold greater infectious virus titre in the lungs, at day 5, compared with the control and wild-type MHV-76 viruses. However, this enhanced viral replication was not observed following infection with the PGK vFLIP viruses. In all cases the vFLIP expressing and control viruses displayed a decreased establishment of splenic latency. The influence of vFLIP on viral replication in an in vitro system has been investigated through the infection of NS0 cells, a murine cell line. These data indicate that the expression of vFLIP, in the context of a herpesvirus infection, increases the initial establishment of a latently infected pool of cells, by up to 3-fold at day 8 post infection. The correlation of this process with the activation of NF-κB has been investigated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.652459  DOI: Not available
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