Interferon prevents formation of replication-competent hepatitis B virus RNA-containing nucleocapsids.
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.
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037.
Stefan F
SF
Wieland
Angelina
A
Eustaquio
Christina
C
Whitten-Bauer
Bryan
B
Boyd
Francis V
FV
Chisari
D000818:Animals; D015139:Blotting, Southern; D002213:Capsid / Q000187:drug effects*; D002460:Cell Line; D004318:Doxycycline; D006515:Hepatitis B virus / Q000378:metabolism*; D016899:Interferon-beta / Q000494:pharmacology*; D051379:Mice; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
C100808:pgRNA; D012313:RNA; D016899:Interferon-beta; D004318:Doxycycline