{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:43:17Z","timestamp":1790836997205,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.pntd.0011098","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T00:00:00Z","timestamp":1675296000000}}],"reference-count":44,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000777","name":"University of Leeds","doi-asserted-by":"crossref","award":["Dean's Research Award"],"award-info":[{"award-number":["Dean's Research Award"]}],"id":[{"id":"10.13039\/501100000777","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["096670\/Z\/11\/Z"],"award-info":[{"award-number":["096670\/Z\/11\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>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\u2032 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\u2019 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 <jats:italic>in vitro<\/jats:italic> translation efficiency and virus infectivity, suggesting that the 5\u2019UTR functions independently to virus translation. Together, these findings reveal distinct RNA elements within the 5\u2032UTR 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.<\/jats:p>","DOI":"10.1371\/journal.pntd.0011098","type":"journal-article","created":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T18:44:05Z","timestamp":1674499445000},"page":"e0011098","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Functional characterization of 5\u2032 untranslated region (UTR) secondary RNA structures in the replication of tick-borne encephalitis virus in mammalian cells"],"prefix":"10.1371","volume":"17","author":[{"given":"Laura","family":"Upstone","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Colley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2906-5513","authenticated-orcid":true,"given":"Niluka","family":"Goonawardane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,1,23]]},"reference":[{"key":"pntd.0011098.ref001","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1007\/s004150050077","article-title":"Tick-borne encephalitis in Sweden in relation to aseptic meningo-encephalitis of other etiology: a prospective study of clinical course and outcome","volume":"244","author":"G G\u00fcnther","year":"1997","journal-title":"Journal of Neurology"},{"key":"pntd.0011098.ref002","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1093\/brain\/122.11.2067","article-title":"The clinical and epidemiological profile of tick-borne encephalitis in southern Germany 1994\u201398: A prospective study of 656 patients","volume":"122","author":"R. 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