Nuclear Import of Hepatitis B Virus Capsids and Genome

Abstract

Hepatitis B virus (HBV) is an enveloped pararetrovirus with a DNA genome, which is found in an up to 36 nm-measuring capsid. Replication of the genome occurs via an RNA intermediate, which is synthesized in the nucleus. The virus must have thus ways of transporting its DNA genome into this compartment. This review summarizes the data on hepatitis B virus genome transport and correlates the finding to those from other viruses.

Keywords: genome release; hepatitis B virus; nuclear pore; nuclear transport; nucleoporin.

Figure 1

Schematic presentation of the nuclear pore complex (NPC) with key structures. Cytoplasm: top, nucleus: bottom of the figure. Nup: nucleoporins.

Figure 2

Model of capsid attachment to the NPC and nuclear genome release of herpesviruses. Cytoplasm: top, karyoplasm: bottom. The capsids are shown as blue icosahedra, the genome as a double waved line in black. Importin β (Impβ): black ellipse. The cellular RNA polymerase, transcribing the immediate early genes is depicted as blue sphere.

Figure 3

Model of capsid attachment to the NPC, capsid dissociation and nuclear genome transport of adenoviruses. Cytoplasm: top, karyoplasm: bottom. The capsids are shown as blue icosahedra, the genome as a double waved line in black. The genome-attached proteins are depicted as red, green and black spheres.

Figure 4

Model of parvoviral capsid attachment to the NPC and local dissociation of the nuclear envelope. Cytoplasm: top, karyoplasm: bottom. The capsids are shown as blue icosahedra, the genome as a single waved, black line.

Figure 5

Hypothetical model of HBV genome transport mediated via the viral polymerase. Cytoplasm: top, karyoplasm: bottom. The capsids are shown as blue icosahedra, the genome as red circle (minus strand DNA) and an incomplete blue circle (plus strand DNA) with the covalently attached polymerase (green sphere). Importin β: black ellipse, importin α: grey ellipse. Core protein dimers are shown as light blue triangles. The model is based on a cytoplasmic capsid disassembly, which could also occur at the NPC. Capsid disassembly would result in core protein dimers, which in turn could re-assemble to empty capsids. These capsids would then be dissociated again upon importin β-binding. Import of the genome in complex with the viral polymerase is shown to occur via importin α/β as no IBB can be identified on the polymerase.

Figure 6

Model of HBV genome transport mediated in intact capsids. Cytoplasm: top, karyoplasm: bottom. The capsids are shown as blue icosahedra, the genome as red circle (minus strand DNA) and an incomplete blue circle (plus strand DNA) with the covalently attached polymerase (green sphere). Importin β: black ellipse, importin α: grey ellipse. Core protein dimers are shown as light blue triangles. The model is based on capsid disassembly in the nuclear basket after capsid Nup153-interaction. Disassembly is restricted to capsids with a mature genome by an unknown mechanism. It leads to release of the polymerase-genome complex and to nuclear core protein dimers, which re-assemble to empty capsids.