Understanding the function and structure of herpes simplex virus type 1 pUL55, a novel immune evasion protein
type: CreativeWork
description: Herpes simplex virus-1 (HSV-1) infects approximately 67% of the human population, causing disease ranging from asymptomatic to severe. The virus affects individuals around the world, and results in lifelong infection. This work focusses on pUL55, a HSV-1 tegument protein, which we hypothesised to be an innate immune modulator with similar functions to ICP0. ICP0 exhibits E3 ubiquitin ligase activity and is known to stimulate proteasomal degradation of several host proteins in HSV-1 infected cells. Multiple studies to date have used the *dl*1403 mutant strain of HSV-1, engineered to lack ICP0, which has demonstrated the importance of ICP0 activity in the establishment of viral infection in multiple model systems. However, a recently generated mutant strain of HSV-1 lacking ICP0 did not recapitulate many of the published characteristics of the well-established *dl*1403 strain. Comparative proteomic analysis had uncovered that the *dl*1403 mutant lacked expression of pUL55 in addition to ICP0. Accordingly, it was hypothesised that the additional loss of pUL55 may be required for some of the observed phenotypes in cells infected with the *dl*1403 mutant. The aim of this research was to identify whether pUL55 has a similar function to ICP0 and investigate the mechanism by which pUL55 can modulate the host proteome. Recombinant viruses lacking pUL55 or lacking both pUL55 and ICP0 were generated and examined for their ability to form plaques on monolayers of cells known to restrict *dl*1403 as well as their ability to degrade specific host proteins that are known to be ICP0 targets. These data demonstrated that viruses lacking either pUL55 or ICP0 individually are able to form plaques effectively on restrictive cells and degrade both PML and IFI16, known targets of ICP0-mediated degradation. Conversely, the newly generated virus lacking both pUL55 and ICP0 was significantly inhibited in its ability to form plaques on restrictive cell monolayers and was unable to degrade PM…
abstract: Herpes simplex virus-1 (HSV-1) infects approximately 67% of the human population, causing disease ranging from asymptomatic to severe. The virus affects individuals around the world, and results in lifelong infection. This work focusses on pUL55, a HSV-1 tegument protein, which we hypothesised to be an innate immune modulator with similar functions to ICP0. ICP0 exhibits E3 ubiquitin ligase activity and is known to stimulate proteasomal degradation of several host proteins in HSV-1 infected cells. Multiple studies to date have used the *dl*1403 mutant strain of HSV-1, engineered to lack ICP0, which has demonstrated the importance of ICP0 activity in the establishment of viral infection in multiple model systems. However, a recently generated mutant strain of HSV-1 lacking ICP0 did not recapitulate many of the published characteristics of the well-established *dl*1403 strain. Comparative proteomic analysis had uncovered that the *dl*1403 mutant lacked expression of pUL55 in addition to ICP0. Accordingly, it was hypothesised that the additional loss of pUL55 may be required for some of the observed phenotypes in cells infected with the *dl*1403 mutant. The aim of this research was to identify whether pUL55 has a similar function to ICP0 and investigate the mechanism by which pUL55 can modulate the host proteome. Recombinant viruses lacking pUL55 or lacking both pUL55 and ICP0 were generated and examined for their ability to form plaques on monolayers of cells known to restrict *dl*1403 as well as their ability to degrade specific host proteins that are known to be ICP0 targets. These data demonstrated that viruses lacking either pUL55 or ICP0 individually are able to form plaques effectively on restrictive cells and degrade both PML and IFI16, known targets of ICP0-mediated degradation. Conversely, the newly generated virus lacking both pUL55 and ICP0 was significantly inhibited in its ability to form plaques on restrictive cell monolayers and was unable to degrade PM…
author: Boparan, Navneet
language: eng
keywords: HSV-1, ICP0, PML, pUL55
license: https://www.repository.cam.ac.uk/bitstreams/5d11eb65-e49b-4590-9545-371c7e9fb2ac/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2024-03-21
date modified: 2026-07-22T22:23:56Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.109933