Article first published online: 14 MAR 2013
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 58, Issue 1, pages 31–42, July 2013
How to Cite
Meier, A., Mehrle, S., Weiss, T. S., Mier, W. and Urban, S. (2013), Myristoylated PreS1-domain of the hepatitis B virus L-protein mediates specific binding to differentiated hepatocytes. Hepatology, 58: 31–42. doi: 10.1002/hep.26181
Potential conflict of interest: Nothing to report.
This work received grants from the Bundesministerium für Bildung und Forschung (BMBF), “Innovative Therapieverfahren,” grant number 01GU0702, the Landesstiftung Baden Württemberg and financial support from the Vision 7 GmbH.
The data presented in this study is consistent with the recent publication of Yan et al. describing sodium taurocholate cotransporting polypeptide (NTCP/SLC10A1) as a specific receptor for HBV and HDV infection. Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, et al. Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. elife 2012;1:e00049.
- Issue published online: 24 JUN 2013
- Article first published online: 14 MAR 2013
- Accepted manuscript online: 5 DEC 2012 02:51AM EST
- Manuscript Accepted: 6 NOV 2012
- Manuscript Received: 11 JUL 2012
Chronic infection with the human hepatitis B virus (HBV) is a global health problem and a main cause of progressive liver diseases. HBV exhibits a narrow host range, replicating primarily in hepatocytes. Both host and hepatocyte specificity presumably involve specific receptor interactions on the target cell; however, direct evidence for this hypothesis is missing. Following the observation that HBV entry is specifically blocked by L-protein-derived preS1-lipopeptides, we visualized specific HBV receptor/ligand complexes on hepatic cells and quantified the turnover kinetics. Using fluorescein isothiocyanate-labeled, myristoylated HBV preS1-peptides we demonstrate (1) the presence of a highly specific HBV receptor on the plasma membrane of HBV-susceptible primary human and tupaia hepatocytes and HepaRG cells but also on hepatocytes from the nonsusceptible species mouse, rat, rabbit and dog; (2) the requirement of a differentiated state of the hepatocyte for specific preS1-binding; (3) the lack of detectable amounts of the receptor on HepG2 and HuH7 cells; (4) a slow receptor turnover at the hepatocyte membrane; and (5) an association of the receptor with actin microfilaments. The presence of the preS1-receptor in primary hepatocytes from some non-HBV-susceptible species indicates that the lack of susceptibility of these cells is owed to a postbinding step. Conclusion: These findings suggest that HBV hepatotropism is mediated by the highly selective expression of a yet unknown receptor* on differentiated hepatocytes, while species specificity of the HBV infection requires selective downstream events, e.g., the presence of host dependency or the absence of host restriction factors. The criteria defined here will allow narrowing down reasonable receptor candidates and provide a binding assay for HBV-receptor expression screens in hepatic cells. (HEPATOLOGY 2013)