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The virus causes tick-borne encephalitis (TBE) in humans, and symptoms range from mild flu-like symptoms to severe and long-lasting sequelae, including permanent brain damage. It has been suggested that within the population of viruses transmitted to the mammalian host, quasispecies with neurotropic properties might become dominant in the host resulting in neurological symptoms. We previously demonstrated the existence of TBEV variants with variable poly(A) tracts within a single blood-fed tick. To characterize the role of the poly(A) tract in TBEV replication and virulence, we generated infectious clones of Tor\u00f6-2003 with the wild-type (A)<jats:sub>3<\/jats:sub>C(A)<jats:sub>6<\/jats:sub> sequence (Tor\u00f6-6A) or with a modified (A)<jats:sub>3<\/jats:sub>C(A)<jats:sub>38<\/jats:sub> sequence (Tor\u00f6-38A). Tor\u00f6-38A replicated poorly compared to Tor\u00f6-6A in cell culture, but Tor\u00f6-38A was more virulent than Tor\u00f6-6A in a mouse model of TBE. Next-generation sequencing of TBEV genomes after passaging in cell culture and\/or mouse brain revealed mutations in specific genomic regions and the presence of quasispecies that might contribute to the observed differences in virulence. These data suggest a role for quasispecies development within the poly(A) tract as a virulence determinant for TBEV in mice.<\/jats:p>","DOI":"10.1038\/srep39265","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T07:00:14Z","timestamp":1481958014000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["The role of the poly(A) tract in the replication and virulence of tick-borne encephalitis virus"],"prefix":"10.1038","volume":"6","author":[{"given":"Naveed","family":"Asghar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Ping","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Lindqvist","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wessam","family":"Melik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Kr\u00f6ger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna K.","family":"\u00d6verby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,12,16]]},"reference":[{"key":"BFsrep39265_CR1","doi-asserted-by":"crossref","unstructured":"Jaenson, T. 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