Chronic viral hepatitis
Molecular biology of hepatitis B viruses
(Prof. Dr. Volker Bruss)
Envelopment of the nucleocapsid
The virus particle is formed by the assembly of an icosahedral capsid containing the viral genome in the cytosol of the hepatocyte and subsequent envelopment of the capsid at an internal cellular membrane containing viral proteins. This envelopment or budding process translocates the capsid across the cellular membrane and allows the release of the infectious virus into the blood stream by the secretion machinery of the cell. A very specific interaction between the capsid surface and cytoplasmic domains of viral membrane proteins are required for and probably drive the envelopment process. We try to describe the molecular surfaces of capsid and envelope involved in budding. In addition we want to use this step as an antiviral target by developing small molecules specifically blocking capsid-envelope interactions.
Maturation of the nucleocapsid
During capsid formation a viral RNA molecule is packaged in the lumen together with a viral reverse transcriptase. This early, RNA containing, "immature" capsid is incompetent for budding. The reverse transcription of the RNA molecule in the capsid lumen generates the viral DNA genome. The capsid is then named "mature" and becomes competent for envelopment. We want to understand the molecular difference between immature and mature capsids and how this envelopment signal is generated.
Formation of the episomal HBV cccDNA genome
After infection the viral DNA genome enters the nucleus and stays there as a covalently closed circular (ccc) molecule in an episomal state. Current therapies of HBV infections are not capable of directly reducing the amount of viral ccc DNA. Therefore, the virus often recurs after cessation of an antiviral therapy. We want to understand the steps leading from the open circular viral DNA genome in the capsid to the ccc DNA form of the genome in the nucleus and the cellular factors involved in this process.
Entry of the hepatitis D virus
The hepatitis D virus (HDV) is a defective virus using the HBV surface proteins for the envelopment of its own nucleoprotein complex containing the HDV RNA genome. Because the entry of a virus into its host cell is governed by the virus’ surface proteins it is assumed that HDV uses the same cellular machinery as HBV to infect hepatocytes. HDV replicated intracellularly much faster than HBV and is therefore a useful tool to study HDV/HBV entry. We are interested to investigate the HDV/HBV entry process which is mainly unsolved.