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© The Rockefeller University Press, 0021-9525/1999//45 $5.00
The Journal of Cell Biology, Volume 145, Number 1, , 1999 45-55

Regular Articles

Phosphorylation-dependent Binding of Hepatitis B Virus Core Particles to the Nuclear Pore Complex



Michael Kann*, Beate Sodeik{ddagger}, Angelika Vlachou*, Wolfram H. Gerlich*, and Ari Helenius{ddagger}

* Institute of Medical Virology, Justus Liebig University, D-35392 Giessen, Germany; and {ddagger} Yale University School of Medicine, Department of Cell Biology, New Haven, Connecticut 06520-8002

Although many viruses replicate in the nucleus, little is known about the processes involved in the nuclear import of viral genomes. We show here that in vitro generated core particles of human hepatitis B virus bind to nuclear pore complexes (NPCs) in digitonin-permeabilized mammalian cells. This only occurred if the cores contained phosphorylated core proteins. Binding was inhibited by wheat germ agglutinin, by antinuclear pore complex antibodies, and by peptides corresponding either to classical nuclear localization signals (NLS) or to COOH-terminal sequences of the core protein. Binding was dependent on the nuclear transport factors importins (karyopherins) {alpha} and β. The results suggested that phosphorylation induces exposure of NLS in the COOH-terminal portion of the core protein that allows core binding to the NPCs by the importin- (karyopherin-) mediated pathway. Thus, phosphorylation of the core protein emerged as an important step in the viral replication cycle necessary for transport of the viral genome to the nucleus.

Key Words: core • hepatitis B virus • nuclear pore • nucleocapsid • phosphorylation

Address correspondence to Dr. Michael Kann, Institute of Medical Virology, Justus Liebig University, Frankfurter Street 107, D-35392 Giessen, Germany. Tel.: 49-641-99-41243. Fax: 49-641-99-41209. E-mail: michael. kann{at}viro.med.uni-giessen.de

1. Abbreviations used in this paper: cccDNA, covalently closed circular DNA; HBV, hepatitis B virus; hHBc, human HepG2.2.15-derived core; hsp, heat shock protein; MALDI, matrix-assisted laser desorption/ionization; NBS, nuclear pore binding signal; NLS, nuclear localization signal; NPC, nuclear pore complex; PKC, protein kinase C; P-rHBc, phosphorylated E. coli–derived cores; rHBc, unphosphorylated E. coli–derived cores; RRL, rabbit reticulocyte lysate; TFA, trifluoroacetic acid.

The present address of B. Sodeik is Institute of Biochemistry, Medical School Hannover, OE4310, D-30623 Hannover, Germany. The present address of A. Helenius is Laboratory for Biochemistry, Swiss Federal Institute of Technology Zürich, CH-8092 Zürich, Switzerland.


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