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Journal of Virology, December 1998, p. 10138-10147, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Host Cell-Virus Cross Talk: Phosphorylation of a Hepatitis B Virus Envelope Protein Mediates Intracellular Signaling

Kirsten Rothmann,1 Martina Schnölzer,2 Gerald Radziwill,3 Eberhard Hildt,4 Karin Moelling,3 and Heinz Schaller1,*

Zentrum für Molekulare Biologie Heidelberg1 and DKFZ,2 D-69124 Heidelberg, and Institut für Experimentelle Chirurgie, Klinikum Rechts der Isar, D-81675 Munich,4 Germany, and Institut für Medizinische Virologie, CH-8028 Zurich, Switzerland3

Received 26 May 1998/Accepted 20 August 1998

Phosphorylation of cytosolic pre-S domains of the duck hepatitis B virus (DHBV) large envelope protein (L) was identified as a regulatory modification involved in intracellular signaling. By using biochemical and mass spectrometric analyses of phosphopeptides obtained from metabolically radiolabeled L protein, a single phosphorylation site was identified at serine 118 as part of a PX(S/T)P motif, which is strongly preferred by ERK-type mitogen-activated protein kinases (MAP kinases). ERK2 specifically phosphorylated L at serine 118 in vitro, and L phosphorylation was inhibited by a coexpressed MAP kinase-specific phosphatase. Furthermore, L phosphorylation and ERK activation were shown to be induced in parallel by various stimuli. Functional analysis with transfected cells showed that DHBV L possesses the ability to activate gene expression in trans and, by using mutations eliminating (Sright-arrowA) or mimicking (Sright-arrowD) serine phosphorylation, that this function correlates with L phosphorylation. These mutations had, however, no major effects on virus production in cell culture and in vivo, indicating that L phosphorylation and transactivation are not essential for hepadnavirus replication and morphogenesis. Together, these data suggest a role of the L protein in intracellular host-virus cross talk by varying the levels of pre-S phosphorylation in response to the state of the cell.

* Corresponding author. Mailing address: Zentrum für Molekulare Biologie Heidelberg, Im Neuenheimer Feld 282, D-69124 Heidelberg, Germany. Phone: 49 6221 54 68 85. Fax: 49 6221 54 58 93. E-mail: hshd{at}zmbh.uni-heidelberg.de.

Journal of Virology, December 1998, p. 10138-10147, Vol. 72, No. 12
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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