{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:54:54Z","timestamp":1791114894980,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2011,5,27]],"date-time":"2011-05-27T00:00:00Z","timestamp":1306454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem\u2013loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.<\/jats:p>","DOI":"10.1093\/nar\/gkr237","type":"journal-article","created":{"date-parts":[[2011,5,29]],"date-time":"2011-05-29T00:14:31Z","timestamp":1306628071000},"page":"7034-7048","source":"Crossref","is-referenced-by-count":29,"title":["Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus"],"prefix":"10.1093","volume":"39","author":[{"given":"A.","family":"Tuplin","sequence":"first","affiliation":[{"name":"School of Life Sciences, University of Warwick, Coventry, CV4 7AL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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