Hoffmann, Jasmin and Boehm, Caroline and Himmelsbach, Kiyoshi and Donnerhak, Christian and Roettger, Hendrik and Weiss, Thomas S. and Ploen, Daniela and Hildt, Eberhard (2013) Identification of alpha-taxilin as an essential factor for the life cycle of hepatitis B virus. JOURNAL OF HEPATOLOGY, 59 (5). pp. 934-941. ISSN 0168-8278, 1600-0641
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Background & Aims: alpha-taxilin was identified as binding partner of syntaxins and is supposed to regulate vesicular trafficking. However, the physiological functions of alpha-taxilin and its potential relevance for the life cycle of hepatitis B virus (HBV) are still poorly understood. Methods: Transfected hepatoma cells, infected primary human hepatocytes, and liver tissue of HBV-infected patients were used to study the expression of alpha-taxilin. Subcellular localization and colocalization were analyzed by confocal laser scanning microscopy (CLSM). Protein-protein interactions were further investigated by co-immunoprecipitations. Silencing of alpha-taxilin expression was performed by lentiviral gene transfer. Results: HBV producing cells show a significant higher level of alpha-taxilin. HBV induces alpha-taxilin expression, by its regulatory proteins HBx and LHBs via c-Raf. This indicates that alpha-taxilin is essential for the release of HBV particles. CLSM and co-immunoprecipitations demonstrated that the PreS1PreS2 domain of LHBs interacts with alpha-taxilin. alpha-taxilin harbors a YXXL motif that represents a classic late domain. In accordance with this, it was found by co-immunoprecipitations that alpha-taxilin interacts with the ESCRT I component tsg101. CLSM revealed that a fraction of alpha-taxilin colocalizes with LHBs and tsg101. Conclusions: alpha-taxilin plays an essential role for release of HBV-DNA containing particles. It might act as an adapter that binds, on the one hand, to LHBs and, on the other hand, to tsg101 and thereby helps recruit the ESCRT machinery to the viral envelope proteins. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN HEPATOCYTES; EXPRESSION; PROTEIN; MORPHOGENESIS; PARTICLES; SYSTEM; CELLS; HBV; REPLICATION; ACTIVATOR; HBV; Signal transduction; HBx; Morphogenesis |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Mar 2020 07:32 |
| Last Modified: | 27 Mar 2020 07:32 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15799 |
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