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Dengue virus (DEN) and other flaviviruses, such as West Nile and yellow fever viruses, contain a 5\u2032 m<jats:sup>7<\/jats:sup>GpppN-capped positive-sense RNA genome with a nonpolyadenylated 3\u2032 untranslated region (UTR) that has been presumed to undergo translation in a cap-dependent manner. However, the means by which the DEN genome is translated effectively in the presence of capped, polyadenylated cellular mRNAs is unknown. This report demonstrates that DEN replication and translation are not affected under conditions that inhibit cap-dependent translation by targeting the cap-binding protein eukaryotic initiation factor 4E, a key regulator of cellular translation. We further show that under cellular conditions in which translation factors are limiting, DEN can alternate between canonical cap-dependent translation initiation and a noncanonical mechanism that appears not to require a functional m<jats:sup>7<\/jats:sup>G cap. This DEN noncanonical translation is not mediated by an internal ribosome entry site but requires the interaction of the DEN 5\u2032 and 3\u2032 UTRs for activity, suggesting a novel strategy for translation of animal viruses.<\/jats:p>","DOI":"10.1128\/jvi.80.6.2976-2986.2006","type":"journal-article","created":{"date-parts":[[2006,2,24]],"date-time":"2006-02-24T20:47:54Z","timestamp":1140814074000},"page":"2976-2986","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":159,"title":["Dengue Virus Utilizes a Novel Strategy for Translation Initiation When Cap-Dependent Translation Is Inhibited"],"prefix":"10.1128","volume":"80","author":[{"given":"Dianna","family":"Edgil","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, School of Public Health, University of California, Berkeley, Berkeley, California 94720-7360"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotta","family":"Polacek","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Public Health, University of California, Berkeley, Berkeley, California 94720-7360"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Harris","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, School of Public Health, University of California, Berkeley, Berkeley, California 94720-7360"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.17.6259-6268.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1504"},{"key":"e_1_3_2_4_2","first-page":"186","volume":"3","year":"1997","unstructured":"Borman, A. 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