Novel cell culture systems to study Hepatitis B (HBV) and Hepatitis delta Virus (HDV) infections

• Applicant: Professor Dr. Stephan Urban
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2012 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 209091148

Chronic infections with HBV and HDV are global health problems. Currently, in vitro studies of both viruses are restricted to primary hepatocytes or HepaRG cells. Using these systems an HBV envelope protein determinant for specific receptor recognition has been identified. It relates to the N-terminal part of the myristoylated preS1 domain of the L-protein and mediates selective binding to hepatocytes. Peptides corresponding to this domain target hepatocytes and abrogate infection in vitro and in vivo. Aiming at the identification of novel cell culture systems for HBV/HDV infection, we screened hepatic cell lines for HBV-receptor expression and susceptibility and identified one cell line (WRL-68) that binds the peptidic ligand and emerged susceptible to HBV and HDV. Based on this finding we here intend to pursue (i) a comprehensive characterization of this novel cell culture system for specific features of infection; (ii) the identification of additional cell lines capable of binding the HBVpreS-ligand, (iii) to analyze cell differentiation and polarization conditions that regulate receptor expression; (iv) comparative analyses of HBV and HDV susceptibility to identify post entry restriction steps of infection; (v) the establishment of persistently infected cell lines that replicate HBV from its authentic cccDNA template (vi) the identification of potential co-infection systems for HBV/HDV and HBV/HCV and the analysis of interdependencies between the different viruses/viral replicons. If successful, we will provide novel HBV/HDV cell culture systems that allow studying novel aspects of virus replication.

• DFG Programme: Research Grants