Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.543357
Title: Virion assembly of the herpes simplex virus type 1 E3 ubiquitin ligase ICP0
Author: Maringer, Kevin
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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Abstract:
Within the herpes simplex virus type 1 particle, a complex compartment termed the tegument is sandwiched between the nucleocapsid and envelope. Interactions between tegument components and the cytoplasmic tails of viral envelope glycoproteins are thought to play some role in the poorly defined process of tegument assembly. Here, virion incorporation of a major tegument protein, VP22, and the immediate-early transactivator of gene expression ICP0 was studied to improve our understanding of herpesvirus morphogenesis. In infected cells VP22 was found to bridge the viral glycoproteins gE and gM to form an assembly complex that also incorporates ICP0. VP22 is the major determinant for ICP0 packaging, although both gE and gM were shown to be required for optimal recruitment of ICP0 into the complex and virion. The glycoproteins are redundant for VP22, but not ICP0, assembly. A conserved region of VP22, and N-terminal sequences known to facilitate VP22 oligomerisation, contribute to complex formation. ICP0 domains important for VP22-ICP0 association and ICP0 assembly include the functionally essential RING finger motif and ICP0’s C-terminus. The immediate-early protein ICP27, known to be required for ICP0 assembly, was shown for the first time to be recruited into virions, independently of VP22 and ICP0. A mutant that packages enhanced levels of ICP0 exhibited augmented growth kinetics, implying that virion ICP0 performs important functions in infection. No impact of VP22 on ICP0 function could be determined, although a new role for VP22 in modulating gene expression was identified. Nevertheless, VP22 mutation modified ICP0 localisation in infected cells. Interestingly, ICP0 was shown to enhance late stages of virus replication. ICP0-mediated ubiquitination within putative cytoplasmic assembly domains was characterised to further investigate this late function. This work significantly improves our understanding of how glycoprotein-tegument interactions lead to the formation of multicomponent assemblies involved in herpesvirus morphogenesis.
Supervisor: Elliott, Gillian Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.543357  DOI: Not available
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