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In the case of mosquito-borne flaviviruses, highly\nconserved cyclization sequences (CS) have been identified, and their\nfunctionality has been experimentally confirmed. Here, we provide an\nexperimental identification of CS elements of tick-borne encephalitis\nvirus (TBEV). These elements, termed 5\u2032-CS-A and\n3\u2032-CS-A, are conserved among various tick-borne flaviviruses,\nbut they are unrelated to the mosquito-borne CS elements and are\nlocated at different genomic positions. The 5\u2032-CS-A element is\nsituated upstream rather than downstream of the AUG start codon and, in\ncontrast to mosquito-borne flaviviruses, it was found that the entire\nprotein C coding region is not essential for TBEV replication. The\ncomplementary 3\u2032-CS-A element is located within the bottom stem\nrather than upstream of the characteristic 3\u2032-terminal\nstem-loop structure, implying that this part of the proposed structure\ncannot be formed when the genome is in its circularized conformation.\nFinally, we demonstrate that the CS-A elements can also mediate their\nfunction when the 5\u2032-CS-A element is moved from its natural\nposition to one corresponding to the mosquito-borne CS. The recognition\nof essential RNA elements and their differences between mosquito-borne\nand tick-borne flaviviruses has practical implications for the design\nof replicons in vaccine and vector development.<\/jats:p>","DOI":"10.1128\/jvi.80.8.4099-4113.2006","type":"journal-article","created":{"date-parts":[[2006,3,29]],"date-time":"2006-03-29T20:47:35Z","timestamp":1143665255000},"page":"4099-4113","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":89,"title":["Functional Analysis of the Tick-Borne Encephalitis Virus Cyclization ElementsIndicates Major Differences between Mosquito-Borne and Tick-Borne Flaviviruses"],"prefix":"10.1128","volume":"80","author":[{"given":"Regina M.","family":"Kofler","sequence":"first","affiliation":[{"name":"Clinical Institute of Virology, Medical University of Vienna"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena M.","family":"Hoenninger","sequence":"additional","affiliation":[{"name":"Clinical Institute of Virology, Medical University of Vienna"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Thurner","sequence":"additional","affiliation":[{"name":"Institute for Theoretical Chemistry, University of Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian W.","family":"Mandl","sequence":"additional","affiliation":[{"name":"Clinical Institute of Virology, Medical University of Vienna"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104248200"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.06.009"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.11.6631-6643.2005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.9.5650-5658.1995"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.48.070179.002521"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.18860-0"},{"key":"e_1_3_2_8_2","first-page":"1043","year":"2001","unstructured":"Burke, D. 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