Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells.
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 outc...
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ftdoajarticles:oai:doaj.org/article:5a1288844aed44c49cfbec6140863941 2023-05-15T15:09:37+02:00 Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells. Laura Upstone Robin Colley Mark Harris Niluka Goonawardane 2023-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011098 https://doaj.org/article/5a1288844aed44c49cfbec6140863941 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0011098 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011098 https://doaj.org/article/5a1288844aed44c49cfbec6140863941 PLoS Neglected Tropical Diseases, Vol 17, Iss 1, p e0011098 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011098 2023-03-05T01:33:15Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic The ''Y'' ENVELOPE(-112.453,-112.453,57.591,57.591) PLOS Neglected Tropical Diseases 17 1 e0011098 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Laura Upstone Robin Colley Mark Harris Niluka Goonawardane Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. |
format |
Article in Journal/Newspaper |
author |
Laura Upstone Robin Colley Mark Harris Niluka Goonawardane |
author_facet |
Laura Upstone Robin Colley Mark Harris Niluka Goonawardane |
author_sort |
Laura Upstone |
title |
Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells. |
title_short |
Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells. |
title_full |
Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells. |
title_fullStr |
Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells. |
title_full_unstemmed |
Functional characterization of 5' untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells. |
title_sort |
functional characterization of 5' untranslated region (utr) secondary rna structures in the replication of tick-borne encephalitis virus in mammalian cells. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011098 https://doaj.org/article/5a1288844aed44c49cfbec6140863941 |
long_lat |
ENVELOPE(-112.453,-112.453,57.591,57.591) |
geographic |
Arctic The ''Y'' |
geographic_facet |
Arctic The ''Y'' |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 1, p e0011098 (2023) |
op_relation |
https://doi.org/10.1371/journal.pntd.0011098 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011098 https://doaj.org/article/5a1288844aed44c49cfbec6140863941 |
op_doi |
https://doi.org/10.1371/journal.pntd.0011098 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
17 |
container_issue |
1 |
container_start_page |
e0011098 |
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1766340781345341440 |