Andreas Untergasser and Uta Zedler contributed equally to this work.
Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection†
Article first published online: 22 FEB 2006
Copyright © 2006 American Association for the Study of Liver Diseases
Volume 43, Issue 3, pages 539–547, March 2006
How to Cite
Untergasser, A., Zedler, U., Langenkamp, A., Hösel, M., Quasdorff, M., Esser, K., Dienes, H.-P., Tappertzhofen, B., Kolanus, W. and Protzer, U. (2006), Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection. Hepatology, 43: 539–547. doi: 10.1002/hep.21048
Potential conflict of interest: Nothing to report.
- Issue published online: 22 FEB 2006
- Article first published online: 22 FEB 2006
- Manuscript Accepted: 28 NOV 2005
- Manuscript Received: 26 JUL 2005
- Deutsche Forschungsgemeinschaft (DFG)
- Köln Fortune; Medical Faculty, University of Cologne
Dendritic cells (DC) of hepatitis B virus (HBV) carriers have been reported to exhibit functional impairment. Possible explanations for this phenomenon are infection of HBV by DC or alteration of DC function by HBV. We therefore analyzed whether DC support the different steps of HBV infection and replication: uptake, deposition of the HBV genome in the nucleus, antigen expression, and progeny virus release. When HBV genomes were artificially introduced into monocyte-derived DC by adenoviral vectors, low-level expression of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) but no HBV replication was detected. When monocyte-derived DC were subjected to wild-type HBV or a recombinant HBV expressing Renilla luciferase under a non–liver-specific promoter, intracellular HBV DNA was detected in a low percentage of cells. However, neither nuclear cccDNA was formed nor luciferase activity was detected, indicating that either uncoating or nucleocytoplasmic transport were blocked. To verify our observation in the in vivo situation, myeloid and plasmacytoid DC were isolated from blood of high viremic HBV carriers, and analyzed by quantitative polymerase chain reaction (PCR) and electron microscopy. Although circulating DC had in vivo been exposed to more than 104 HBV virions per cell, HBV genomic DNA was hardly detected, and no nuclear cccDNA was detected at all. By using electron microscopy, subviral particles were found in endocytic vesicles, but virions were undetectable as were viral capsids in the cytoplasm. In conclusion, circulating DC may take up HBV antigens, but neither support nucleocytoplasmic transport nor replication of HBV. (HEPATOLOGY 2006;43:539–547.)