Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.798577
Title: Vaccinia virus requires heat-shock proteins for genome replication and virion assembly
Author: Mok, Harriet G. W.
ISNI:       0000 0004 8507 8316
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Abstract:
The large double-stranded DNA virus, vaccinia virus (VACV), is closely related to variola virus, the causative agent of smallpox. While the poxvirus lifecycle has been studied for over 50 years, much is still unknown about the complex multi-step process of genome uncoating. Viral and cellular factors involved in poxvirus uncoating have been identified, including host cell proteasomes, ubiquitin, and heat-shock proteins (HSPs), which play a critical role in protein folding and the prevention of protein aggregation. Although HSPs have been linked to the lifecycle of many viruses including VACV, the role of these proteins in poxvirus infection has not been defined. Using various small compound inhibitors and RNAi, in combination with a battery of virus-specific assays, I show that heat-shock proteins are required for multiple stages of the VACV lifecycle. I demonstrate that Hsp90 is required for two stages of infection: release of the genome from the viral core and assembly of new virions. Following the finding that HSF1, the transcription factor for inducible HSPs, is required for infection, I also identify the Hsp105 as the inducible HSP required for post-replication formation of nascent virions. Given the clinical relevance of HSP inhibitors these results highlight HSPs as potential anti-poxviral drug targets. Collectively, through this work I define new cell factors required for poxvirus infection and demonstrate that subjugation of cellular HSPs during the poxvirus lifecycle is far more complex than previously appreciated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.798577  DOI: Not available
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