Project Description

TP15: Hepatitis B virus X-protein-mediated transcriptional regulation and stability of cccDNA

Hepatitis B Virus (HBV) causes persistent infections of the liver. The template of HBV is a nuclear episome called cccDNA. Transcription of viral genes from cccDNA is regulated by the HBV X-protein through a mostly unknown mechanism probably counteracting epigenetic silencing processes. In addition to this process, cccDNA might vanish during cell division. Based on previous results showing that HBx-mediated activation of cccDNA-transcription requires DDB1 we aim at elucidating further details of this regulation. We will also apply NTCP-expressing cell lines to study cccDNA stability during cell division and determine the contribution of this process to its clearance.
Lempp FA, Urban S. 2017. Hepatitis Delta Virus: Replication Strategy and Upcoming Therapeutic Options for a Neglected Human Pathogen. Viruses. 9(7). pii: E172. doi: 10.3390/v9070172. Review.
Tu T, Budzinska MA, Shackel NA, Urban S. H. 2017. BV DNA Integration: Molecular Mechanisms and Clinical Implications. Viruses. 9(4). pii: E75. doi: 10.3390/v9040075. Review.
Lempp FA, Wiedtke E, Qu B, Roques P, Chemin I, Vondran FW, Le Grand R, Grimm D, Urban S. 2017. Sodium taurocholate cotransporting polypeptide is the limiting host factor of Hepatitis B Virus infection in macaque and pig hepatocytes. Hepatology. 2017 Feb 13. doi: 10.1002/hep.29112.
Hoh A, Heeg M, Ni Y, Schuch A, Binder B, Hennecke N, Blum HE, Nassal M, Protzer U, Hofmann M, Urban S, Thimme R. 2015. HBV-infected HepG2hNTCP cells serve as a novel immunological tool to analyse the antiviral efficacy of CD8+ T cells in vitro. J Virol 89:7433-8
Slijepcevic D, Kaufman C, Wichers CG, Giglioni EH, Lempp F, Duijst S, de Waart DR, Oude Elferink RP, Mier W, Stieger B, Beuers U, Urban S, van de Graaf SF. 2015. Impaired uptake of conjugated bile acids and Hepatitis B Virus pres1-binding in Na+-taurocholate cotransporting polypeptide knockout mice. Hepatology. 62(1):207-19. doi: 10.1002/hep.27694.
Urban S, Bartenschlager R, Kubitz R, Zoulim F. 2014. Strategies to Inhibit Entry of HBV and HDV into Hepatocytes. Gastroenterology 147:48-64.
Ni Y, Lempp FA, Mehrle S, Nkongolo S, Kaufman C, Fälth M, Nassal M, Kubitz, R, Sültmann H, Urban S. 2014. Hepatitis B and D virus exploits sodium taurocholate co-transporting polypeptide (NTCP) for entering hepatocytes in a species-specific manner. Gastroenterology 146:1070-83.
Nkongolo S, Ni Y, Lempp FA, Kaufman C, Lindner T, Esser-Nobis K, Lohmann V, Mier W, Mehrle S, Urban S. 2014. Cyclosporin A inhibits Hepatitis B and Hepatitis D Virus entry by Cyclophilin-independent interference with sodium taurocholate co-transporting polypeptide (NTCP) receptor. J Hepatol 60:723-31.
Urban S, Bogomolov P, Voronkova N, Allweis L, Dandri M, Schwab M, Lempp FA, Haag M, Wedemeyer H, Alexandrov A. 2014. A proof-of-concept Phase IIa clinical trial with the HBV/HDV entry inhibitor Myrcludex B. Hepatology 60 (Suppl): LB20.
Schulze A, Mills, K, Weiss TS, Urban S. 2012. Hepatocyte polarization is essential for the productive entry of the hepatitis B virus. Hepatology 55:373-383.
Petersen J, Dandri M, Mier W, Lütgehetman M, Volz T, von Weizsäcker F, Haberkorn U, Fischer L, Pollock JM, Erbes B, Seitz S, Urban S. 2008. Prevention of hepatitis B virus infection in vivo by entry inhibitors derived from the large envelope protein. Nature Biotechnology 26:335-341.
Gripon P, Rumin S, Urban S, Le Seyec J, Glaise D, Cannie I, Guyomard C, Lucas J, Trepo C, Guguen- Guillouzo C. 2002. Infection of a human hepatoma cell line by hepatitis B virus. PNAS, USA 99:15655-60.
Urban S, Hildt E, Eckerskorn C, Sirma H, Kekule A, Hofschneider PH. 1997. Isolation and characterization of hepatitis B virus X-protein from a baculovirus expression system. Hepatology 26:1045-53.