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In chimpanzees, failure of CD8<jats:sup>+<\/jats:sup> T cells to control HCV replication has been associated with acquisition of mutations in MHC class I\u2010restricted epitopes. In humans, although selection of escape mutations in an immunodominant CTL epitope has been recently described, the overall impact of immune escape during acute HCV infection is unclear. Here, by performing an in depth analysis of the relationship between early cellular immune responses and viral evolution in a chronically evolving HCV acutely infected individual, we demonstrate: (i) the presence of a potent and focused CD8<jats:sup>+<\/jats:sup> T cell response against a novel epitope in the NS3 protein, (ii) the elimination of the quasi\u2010species harboring the original amino acid sequence within this epitope, and (iii) the selection for a virus population bearing amino acid changes at a single residue within the cytotoxic T cell epitope that strongly diminished T cell recognition. These results support the view that acute\u2010phase CD8<jats:sup>+<\/jats:sup> T cell responses exert a biologically relevant pressure on HCV replication and that viruses escaping this host response could have a significant survival advantage.<\/jats:p>","DOI":"10.1002\/eji.200526067","type":"journal-article","created":{"date-parts":[[2005,8,22]],"date-time":"2005-08-22T11:46:27Z","timestamp":1124711187000},"page":"2627-2637","source":"Crossref","is-referenced-by-count":33,"title":["Positive selection of cytotoxic T lymphocyte escape variants during acute hepatitis C virus infection"],"prefix":"10.1002","volume":"35","author":[{"given":"Silvia","family":"Guglietta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna\u2004Rosa","family":"Garbuglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Pacciani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiano","family":"Scott\u00e0","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria\u2004Paola","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Laurenti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enea","family":"Spada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfonso","family":"Mele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria\u2004Rosaria","family":"Capobianchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Taliani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Folgori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Vitelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lionello","family":"Ruggeri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Nicosia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enza","family":"Piccolella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Del Porto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,9,6]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(95)91691-1"},{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118842"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.9.1499"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/315450"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.194.10.1395"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4141(200009)30:9<2479::AID-IMMU2479>3.0.CO;2-B"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2003.037788"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80044-8"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00245-X"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041006"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(98)00102-5"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.24.12584-12595.2002"},{"key":"e_1_2_7_13_2","first-page":"418","article-title":"Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions.","volume":"3","author":"Nei M.","year":"1986","journal-title":"Mol. 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