Intracellular transport of hepatitis B virus

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 alpha and beta. Importin alpha 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 alpha interacts with importin beta 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.

Figure 1

Participation of microtubules and microfilaments in transport processes. Transport processes are indicated as bold arrows. Microtubules (MT, bold lines) have a highly dynamic plus-end and a less dynamic minus-end that is located at the microtubule-organizing (MTOC). They participate in the transport of (1) organelles, e.g. endosomes, (2) direct retrograde transport of capsids via the dynein motor protein complex (adenovirus, HSV 1, parvoviruses), (3) direct anterograde transport of progeny HSV 1 capsids by conventional kinesin, and (4) participate in chromosome segregation upon mitosis. Microfilaments (MF), depicted as dotted lines participate (5) in separation of endocytotic vesicles from the plasma membrane and (6) via polymerization in transport of e.g. Listeria monocytogenes and nuclear polyhedrosis virus (NPV).

Figure 2

Hepadnaviral trafficking within the cell. Capsids are drawn as grey icosahedra. Immat-Capsid, immature capsid, Mat-Capsid, mature capsid. The nucleic acid found within the capsids is depicted as a dotted line (RNA) or a full line (DNA). The arrows present movements (2, 4, 5, 8) or changes of the capsid (1, 7, 9, 10). Further explanations are given in the text.