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Proc Natl Acad Sci U S A. 2005 Jul 12;102(28):9913-7. Epub 2005 Jul 1.

Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids.

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  • 1Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037.


We have previously shown that IFN-beta 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-beta 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-beta or IFN-gamma 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.

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