Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids
Abstract
We have previously shown that IFN-β inhibits hepatitis B virus (HBV) replication by noncytolytic mechanisms that either destabilize pregenomic (pg)RNA-containing capsids or prevent their assembly. Using immortalized murine hepatocyte cell lines stably transfected with a doxycycline (dox)-inducible HBV replication system, we now show that replication-competent pgRNA-containing capsids are not produced when the cells are pretreated with IFN-β before HBV expression is induced with dox. Furthermore, the turnover rate of preformed HBV RNA-containing capsids is not changed in the presence of IFN-β or IFN-γ under conditions in which further pgRNA synthesis is inhibited by dox removal. In summary, these results demonstrate that types 1 and 2 IFN activate hepatocellular mechanism(s) that prevent the formation of replication-competent HBV capsids and, thereby, inhibit HBV replication.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- July 2005
- DOI:
- 10.1073/pnas.0504273102
- Bibcode:
- 2005PNAS..102.9913W
- Keywords:
-
- antiviral;
- β;
- interferon γ;
- MICROBIOLOGY, BIOLOGICAL SCIENCES