Adeyemi, OO orcid.org/0000-0002-0848-5917, Sherry, L orcid.org/0000-0002-4367-772X, Ward, JC et al. (4 more authors) (2019) Involvement of a Nonstructural Protein in Poliovirus Capsid Assembly. Journal of Virology, 93 (5). e01447-18. ISSN 0022-538X
Abstract
Virus capsid proteins must perform a number of roles. These include the ability to self–assemble and to maintain stability under challenging environmental conditions, while retaining the conformational flexibility necessary to uncoat and deliver the viral genome into a host cell. Fulfilling these roles could place conflicting constraints on the innate abilities encoded within the protein sequences. In a previous study, we identified a number of mutations within the capsid coding sequence of poliovirus (PV) that were established in the population during selection for greater thermostability by sequential treatment at progressively higher temperatures. Two mutations in the VP1 protein acquired at an early stage were maintained throughout this selection procedure. One of these mutations prevented virion assembly when introduced into a wild type (wt) infectious clone. Here, we show by sequencing beyond the capsid coding region of the heat selected virions, that two mutations had arisen within the coding region for the 2A protease. Both mutations were maintained throughout the selection process. Introduction of these mutations into a wt infectious clone by site-directed mutagenesis considerably reduced replication. However, they permitted a low level of assembly of infectious virions containing the otherwise lethal mutation in VP1. The 2Apro mutations were further shown to slow the kinetics of viral polyprotein processing and we suggest that this delay improves the correct folding of the mutant capsid precursor protein to permit virion assembly.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019 Adeyemi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. (https://creativecommons.org/licenses/by/4.0/) |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Molecular Virology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 20 Dec 2018 17:02 |
Last Modified: | 12 Jun 2019 00:44 |
Status: | Published |
Publisher: | American Society for Microbiology |
Identification Number: | 10.1128/JVI.01447-18 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:140010 |