Use this URL to cite or link to this record in EThOS:
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
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
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:  DOI: Not available