{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T19:54:58Z","timestamp":1778615698535,"version":"3.51.4"},"reference-count":51,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,1,15]]},"abstract":"<jats:p>Although it is well established that the release of HCV (hepatitis C virus) occurs through the secretory pathway, many aspects concerning the control of this process are not yet fully understood. \u03b1-Taxilin was identified as a novel binding partner of syntaxin-4 and of other members of the syntaxin family, which are part of SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) complexes and so are involved in intracellular vesicle traffic. Since \u03b1-taxilin prevents t-SNARE (target SNARE) formation by binding exclusively to free syntaxin-4, it exerts an inhibitory effect on the vesicular transport. HCV-replicating Huh7.5 cells and HCV-infected primary human hepatocytes and liver samples of patients suffering from chronic HCV contain significantly less \u03b1-taxilin compared with the controls. HCV impairs the expression of \u03b1-taxilin via NS5A-dependent interruption of the Raf\/MEK [MAPK (mitogen-activated protein kinase)\/ERK (extracellular-signal-regulated kinase) kinase] signal transduction cascade. Moreover, the half-life of \u03b1-taxilin is significantly reduced in HCV-replicating cells. Whereas modulation of \u03b1-taxilin expression does not significantly affect genome replication, the overexpression of \u03b1-taxilin prevents the release of HCV. In contrast with this, silencing of \u03b1-taxilin expression leads to increased release of infectious viral particles. This is due to the negative effect of \u03b1-taxilin on t-SNARE formation that leads to impaired vesicular trafficking. Accordingly, overexpression of the t-SNARE component syntaxin-4 increases release of HCV, whereas silencing leads to an impaired release. These data identify \u03b1-taxilin as a novel factor that controls the release of HCV and reveal the mechanism by which HCV controls the activity of \u03b1-taxilin.<\/jats:p>","DOI":"10.1042\/bj20150717","type":"journal-article","created":{"date-parts":[[2015,11,3]],"date-time":"2015-11-03T03:04:01Z","timestamp":1446519841000},"page":"145-155","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Characterization of \u03b1-taxilin as a novel factor controlling the release of hepatitis C virus"],"prefix":"10.1042","volume":"473","author":[{"given":"Fabian","family":"Elgner","sequence":"first","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Donnerhak","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimei","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Medvedev","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9","family":"Schreiber","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenz","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Heilmann","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Ploen","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Himmelsbach","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Malin","family":"Finkernagel","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Klingel","sequence":"additional","affiliation":[{"name":"Department of Molecular Pathology, University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eberhard","family":"Hildt","sequence":"additional","affiliation":[{"name":"Department of Virology, Paul-Ehrlich-Institut, Paul-Ehrlich-Stra\u00dfe 51\u201359, 63225 Langen, Germany"},{"name":"Deutsches Zentrum f\u00fcr Infektionsforschung (DZIF), Inhoffenstra\u00dfe 7, 38124 Braunschweig, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2016,1,5]]},"reference":[{"key":"2021112216315170700_B1","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1038\/nature04077","article-title":"Unravelling hepatitis C virus replication from genome to function","volume":"436","author":"Lindenbach","year":"2005","journal-title":"Nature"},{"key":"2021112216315170700_B2","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1111\/j.1478-3231.2008.01934.x","article-title":"The global burden of hepatitis C","volume":"29","author":"Lavanchy","year":"2009","journal-title":"Liver Int."},{"key":"2021112216315170700_B3","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.tim.2010.11.005","article-title":"Assembly of infectious hepatitis C virus particles","volume":"19","author":"Bartenschlager","year":"2011","journal-title":"Trends Microbiol."},{"key":"2021112216315170700_B4","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1021\/jm401401n","article-title":"On the history of hepatitis C virus cell culture systems","volume":"57","author":"Lohmann","year":"2014","journal-title":"J. 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