Kendall, C, Khalid, H, Müller, M et al. (5 more authors) (2019) Structural and phenotypic analysis of Chikungunya virus RNA replication elements. Nucleic Acids Research, 47 (17). pp. 9296-9312. ISSN 0305-1048
Abstract
Chikungunya virus (CHIKV) is a re-emerging, pathogenic Alphavirus transmitted to humans by Aedes spp. mosquitoes. We have mapped the RNA structure of the 5′ region of the CHIKV genome using selective 2′-hydroxyl acylation analysed by primer extension (SHAPE) to investigate intramolecular base-pairing at single-nucleotide resolution. Taking a structure-led reverse genetic approach, in both infectious virus and sub-genomic replicon systems, we identified six RNA replication elements essential to efficient CHIKV genome replication - including novel elements, either not previously analysed in other alphaviruses or specific to CHIKV. Importantly, through a reverse genetic approach we demonstrate that the replication elements function within the positive-strand genomic copy of the virus genome, in predominantly structure-dependent mechanisms during efficient replication of the CHIKV genome. Comparative analysis in human and mosquito-derived cell lines reveal that a novel element within the 5′UTR is essential for efficient replication in both host systems, while those in the adjacent nsP1 encoding region are specific to either vertebrate or invertebrate host cells. In addition to furthering our knowledge of fundamental aspects of the molecular virology of this important human pathogen, we foresee that results from this study will be important for rational design of a genetically stable attenuated vaccine.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit http://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) The University of Leeds > Faculty of Medicine and Health (Leeds) |
Funding Information: | Funder Grant number Royal Society RG140704 MRC (Medical Research Council) MR/N01054X/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 17 Jul 2019 13:38 |
Last Modified: | 20 Jan 2021 16:13 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/nar/gkz640 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:148663 |