A role for myotubularins in vaccinia virus egress
type: CreativeWork
description: Vaccinia virus (VACV) generates multiple distinct forms of infectious virus. Intracellular mature virus (IMV) particles are surrounded by a single lipid membrane and are mostly released upon lysis of the infected cell. Some IMVs are wrapped by an additional double membrane to form intracellular enveloped virus (IEV), also called wrapped virus (WV). IEVs are transported on microtubules to the cell surface where the outer membrane fuses with the plasma membrane (PM) to expose a double enveloped virion outside the cell. Extracellular enveloped virus (EEV) and CEV are surrounded by two membranes and are morphologically indistinguishable, but whereas EEV are released from the cell to mediate long range virus spread, CEV are retained on the cell surface and induce the formation of actin tails to propel virions to neighbouring cells. EEV and CEV are essential for efficient virus spread within the host. This thesis concerns viral and cellular factors that influence transport of IEV particles from the site of wrapping to the cell membrane. For transport to the cell surface, IEVs rely on active microtubular transport, mediated by the cellular motor protein kinesin-I and the viral proteins E2, F12, which form a complex, and A36. While some of the players in this process are known, other aspects remain elusive, such as the mechanism by which E2/F12 are recruited to IEV, because they lack transmembrane regions. To study factors affecting IEV egress, a proteomic study was performed with A36, E2 and F12 as bait, and many potential interaction partners were identified. Amongst them, two cellular phosphoinositide (PI) phosphatases, myotubularin related protein (MTMR) 1 and su(var), enhancer of zeste, trithorax (SET)-binding factor (SBF) 1 were identified as major hits for the joint interactome of E2 and F12. This thesis has investigated the potential role of these and other cellular proteins in IEV egress. MTMR1 and SBF1 both co-precipitated with E2 and F12 only when both viral prot…
abstract: Vaccinia virus (VACV) generates multiple distinct forms of infectious virus. Intracellular mature virus (IMV) particles are surrounded by a single lipid membrane and are mostly released upon lysis of the infected cell. Some IMVs are wrapped by an additional double membrane to form intracellular enveloped virus (IEV), also called wrapped virus (WV). IEVs are transported on microtubules to the cell surface where the outer membrane fuses with the plasma membrane (PM) to expose a double enveloped virion outside the cell. Extracellular enveloped virus (EEV) and CEV are surrounded by two membranes and are morphologically indistinguishable, but whereas EEV are released from the cell to mediate long range virus spread, CEV are retained on the cell surface and induce the formation of actin tails to propel virions to neighbouring cells. EEV and CEV are essential for efficient virus spread within the host. This thesis concerns viral and cellular factors that influence transport of IEV particles from the site of wrapping to the cell membrane. For transport to the cell surface, IEVs rely on active microtubular transport, mediated by the cellular motor protein kinesin-I and the viral proteins E2, F12, which form a complex, and A36. While some of the players in this process are known, other aspects remain elusive, such as the mechanism by which E2/F12 are recruited to IEV, because they lack transmembrane regions. To study factors affecting IEV egress, a proteomic study was performed with A36, E2 and F12 as bait, and many potential interaction partners were identified. Amongst them, two cellular phosphoinositide (PI) phosphatases, myotubularin related protein (MTMR) 1 and su(var), enhancer of zeste, trithorax (SET)-binding factor (SBF) 1 were identified as major hits for the joint interactome of E2 and F12. This thesis has investigated the potential role of these and other cellular proteins in IEV egress. MTMR1 and SBF1 both co-precipitated with E2 and F12 only when both viral prot…
author: Gali Macedo, Ana
language: eng
keywords: cellular lipids, enveloped virus, membrane identity, myotubularins, phosphoinositides, poxvirus, vaccinia virus, virus egress
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/ace04d3b-7439-40c1-b3ab-8e2df6422c49/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2023-12-31
date modified: 2026-07-22T22:24:21Z
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.109565