Sub-Projects of SFB 535
Invasion and Replication Strategies of Pathogenes
<< back  
SFB Homepage Organisation / Contact Members Announcements
Research Program Sub-Projects Publications Current
Workbench Public Seminars Internal Seminars Search
SP B5

Intracellular Transport and Release of
Hepatitis B Virus Genom



HDoz. Dr. Michael Kann
Institut für Medizinische Virologie (FB 11), Justus-Liebig-Universität, Gießen


Summary

The replication of the hepatitis B virus (HBV) genome occurs within the nucleus via an RNA intermediate. Thus the transport of the genome through cytoplasm and nuclear pore is essential. During the last years we could show that all these transport steps are mediated by the viral capsid, which encloses the genome. The different transport steps are correlated with genome maturation and are facilitated by interactions between the capsid and different cellular proteins. Essential is a structural change of the capsid protein, which leads to translocation of the C-terminus from the lumen of the capsid to the surface. This domain interacts with the cellular microtubules (MT), which transport the capsid to the periphery of the nucleus. Using inhibitors we showed that this transport did not follow the established pathway of other known substrates as e.g. adenoviruses but used a strategy of the human suppressor protein p53 and STATs (Signal transducers and activators of transcription).

The passage through the nuclear pores is mediated by the cellular transport receptors importin a and ß. The corresponding nuclear localization signal (NLS) was identified to be part of the exposed C-terminus. However, after dissociation of the transport receptors from the capsid, it interacts with the nucleoporin 153 that is part of the nuclear basket. This interaction facilitates arrest of the capsids inside the nuclear pore and prevents diffusion deeper into the karyoplasm as it occurs for other karyophilic cargos. Exclusively capsids with a mature DNA genome disintegrate within the basket into capsid protein dimers. These dimers however show a higher affinity to RNA than to DNA so that they re-assemble to capsids including cellular RNA. In future the molecular interactions of the intracytoplasmic transport and of the genome release shall be investigated.

>> Publications
 
SFB Homepage Organisation / Contact Members Announcements
Research Program Sub-Projects Publications Current
Workbench Public Seminars Internal Seminars Search
<< back | ^ Top of Page