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J Virol, April 1998, p. 2600-2606, Vol. 72, No. 4
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Glucagon Treatment Interferes with an Early Step of Duck Hepatitis B Virus Infection

Marc Hild,dagger Olaf Weber,Dagger and Heinz Schaller*

Zentrum für Molekulare Biologie (ZMBH), Universität Heidelberg, 69120 Heidelberg, Germany

Received 5 September 1997/Accepted 12 December 1997

The effect of glucagon on the establishment of hepadnavirus infection was studied in vitro with the duck hepatitis B virus (DHBV) model. The presence of the peptide hormone throughout infection or starting up to 8 h after virus uptake resulted in a dose-dependent reduction in the levels of intra- and extracellular viral gene products and of secreted virions. Treatment with forskolin or dibutyryl-cyclic AMP, two drugs that also stimulate the cyclic AMP (cAMP) signal transduction pathway, resulted in comparable inhibition, suggesting that the inhibitor effect is related to changes in the activity of protein kinase A. In persistently infected hepatocytes, only a slight, but continuous, decrease in viral replication was observed upon prolonged drug treatment. Time course analysis, including detection of DHBV covalently closed circular (ccc) DNA templates, revealed that glucagon acts late during the establishment of infection, at a time when the virus is already internalized, but before detectable ccc DNA accumulation in the nucleus. These data suggest that nuclear import (and reimport) of DHBV DNA genomes from cytosolic capsids is subject to cAMP-mediated regulation by cellular factors responding to changes in the state of the host cell.

* Corresponding author. Mailing address: ZMBH, University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. Phone: 49 6221 54 68 85. Fax: 49 6221 54 58 93. E-mail: hshd{at}zmbh.uni-heidelberg.de.

dagger Present address: Max-Planck-Institut für Immunbiologie, 79108 Freiburg, Germany.

Dagger Present address: Bayer AG, 42096 Wuppertal, Germany.




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