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World J Gastroenterol. Jan 7, 2007; 13(1): 39-47
Published online Jan 7, 2007. doi: 10.3748/wjg.v13.i1.39
Intracellular transport of hepatitis B virus
Michael Kann, André Schmitz, Birgit Rabe
Michael Kann, CNRS-REGER (UMR 5097), Université Bordeaux 2, 146 rue Léo Saignat, F-33076 Bordeaux Cedex, France
André Schmitz, Birgit Rabe, Institute of Medical Virology, Frankfurter Str. 107, D-35392 Giessen, Germany
Author contributions: All authors contributed equally to the work.
Supported by the Deutsche Forschungsgemeinschaft (DFG; SFB 535 TP B5, DFG KA 1193/5-2 and Graduiertenkolleg “Biochemie von Nukleoproteinkomplexen”), by the European Community (‘Combined immune and gene therapy for chronic hepatitis’ 5th call for Quality of Life and Management of Living Resources, Key Action 2, Control of infectious diseases) and the Canadian Institute of Health Research and the Natural Sciences and Engineering Research Council of Canada
Correspondence to: Michael Kann, MD, CNRS-REGER (UMR 5097), Bat 3A, Université Bordeaux 2, 146 rue Léo Saignat, F-33076 Bordeaux Cedex, France. michael.kann@u-bordeaux2.fr
Telephone: +33-5-57574876 Fax: +33-5-57571766
Received: August 3, 2006
Revised: September 25, 2006
Accepted: November 21, 2006
Published online: January 7, 2007
Abstract

For genome multiplication hepadnaviruses use the transcriptional machinery of the cell that is found within the nucleus. Thus the viral genome has to be transported through the cytoplasm and nuclear pore. The intracytosolic translocation is facilitated by the viral capsid that surrounds the genome and that interacts with cellular microtubules. The subsequent passage through the nuclear pore complexes (NPC) is mediated by the nuclear transport receptors importin α and β. Importin α binds to the C-terminus of the capsid protein that comprises a nuclear localization signal (NLS). The exposure of the NLS is regulated and depends upon genome maturation and/or phosphorylation of the capsid protein. As for other karyophilic cargos using this pathway importin α interacts with importin β that facilitates docking of the import complex to the NPC and the passage through the pore. Being a unique strategy, the import of the viral capsid is incomplete in that it becomes arrested inside the nuclear basket, which is a cage-like structure on the karyoplasmic face of the NPC. Presumably only this compartment provides the factors that are required for capsid disassembly and genome release that is restricted to those capsids comprising a mature viral DNA genome.

Keywords: Hepatitis B virus; Capsid; Intracellular transport; Microtubules; Nuclear pore; Importin; Nuclear localization signal; Nuclear basket