Upstone, L, Colley, R, Harris, M orcid.org/0000-0002-9821-1003 et al. (1 more author) (2023) Functional characterization of 5′ untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells. PLoS Neglected Tropical Diseases, 17 (1). e0011098. ISSN 1935-2727
Abstract
Tick-borne Encephalitis Virus (TBEV) is an emerging flavivirus that causes neurological disorders including viral encephalitis of varying severity. Whilst secondary RNA structures within the 5′ untranslated regions (UTRs) of many flaviviruses determine both virus replication and pathogenic outcomes in humans, these elements have not been systematically investigated for TBEV. In this study, we investigated the role of predicted RNA secondary elements of the first 107 nucleotides (nts) of the viral genome forming the stem-loop A (SLA). Experiments were performed in replicons and infectious TBEV system. This region comprises three distinct structures: 5’ stem 0 (S0), stem-loop 1 (SL1) and stem-loop 2 (SL2). S0 was found to be essential for virus infection as mutations in the lower stem of this region significantly reduced virus replication. Point mutations in SL1 that preserved the Y-shape confirmation delayed viral RNA replication but did not abolish virus infectivity. Deletion of SL2 did not abolish infectivity but had a negligible effect on virus propagation. No correlation was observed between in vitro translation efficiency and virus infectivity, suggesting that the 5’UTR functions independently to virus translation. Together, these findings reveal distinct RNA elements within the 5′UTR that are essential for the stability and replication of viral RNA. We further identify changes in RNA folding that lead to altered TBEV infectivity and pathogenesis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 Upstone et al. This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC 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) > Virology 1 (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Feb 2023 09:24 |
Last Modified: | 16 Feb 2023 14:28 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | 10.1371/journal.pntd.0011098 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:196328 |