Hepatitis B Virus

 

About 350 million people are chronically infected with the Hepatitis B Virus (HBV) which is one of the major causes for the incidence of hepatocellular carninomas. HBV is a small DNA-Virus within the Hepadnaviridae family and posesses a circular 3.2 kb partially double-stranded genome. After binding and invading the host cell via a so far unknown receptor, the viral DNA genome is transported to the nucleus and rearranged into the so-called covalently closed circular DNA (cccDNA) representing the matrix for transcription of viral RNAs. The HBV genome only contains four partially overlapping open reading frames of which the X-gene is translated independently of all other proteins. It codes for a highly conserved 154 amino acid protein (HBx, 17 kDa) with unknown function so far.
According to recent studies, HBx interacts with several viral and host cell proteins and therefore is postulated to have multifunctional regulatory functions during HBV replication. Recombinant expression of HBx has already been performed, but no high-resolution structure is available, probably due to high flexibility of the protein. HBx is postulated to be a mediator for interactions of different factors with the cccDNA which at first requires a high conformational flexibility. After complexation of binding partners a conformational change into a specific structure of the HBx might by induced. Also in avian Hepatitis B viruses a gene sequence with high homology to human HBx could be identified, however, with a significant smaller size of only 87 amino acids in the encoded protein.
Aim of this project is the comparing structural analysis of human and avian HBx proteins as well as its interactions with potential binding partners. A structural understanding of the dynamic complex formation will contribute to elucidate the function of HBx and thereby provide new approaches for compounds and therapies agains HBV-infections.

Contact person for this project: Anne Sommer