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Journal of Virology, October 1998, p. 8089-8097, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Avian Hepatitis B Virus Infection Is Initiated by the Interaction of a Distinct Pre-S Subdomain with the Cellular Receptor gp180

Stephan Urban, Klaus M. Breiner, Frank Fehler,dagger Ursula Klingmüller,Dagger and Heinz Schaller*

Zentrum für Molekulare Biologie, Universität Heidelberg, 69120 Heidelberg, Germany

Received 10 April 1998/Accepted 23 June 1998

Functionally relevant hepadnavirus-cell surface interactions were investigated with the duck hepatitis B virus (DHBV) animal model by using an in vitro infection competition assay. Recombinant DHBV pre-S polypeptides, produced in Escherichia coli, were shown to inhibit DHBV infection in a dose-dependent manner, indicating that monomeric pre-S chains were capable of interfering with virus-receptor interaction. Particle-associated pre-S was, however, 30-fold more active, suggesting that cooperative interactions enhance particle binding. An 85-amino-acid pre-S sequence, spanning about half of the DHBV pre-S chain, was characterized by deletion analysis as essential for maximal inhibition. Pre-S polypeptides from heron hepatitis B virus (HHBV) competed DHBV infection equally well despite a 50% difference in amino acid sequence and a much-reduced infectivity of HHBV for duck hepatocytes. These observations are taken to indicate (i) that the functionality of the DHBV pre-S subdomain, which interacts with the cellular receptor, is determined predominantly by a defined three-dimensional structure rather than by primary sequence elements; (ii) that cellular uptake of hepadnaviruses is a multistep process involving more than a single cellular receptor component; and (iii) that gp180, a cellular receptor candidate unable to discriminate between DHBV and HHBV, is a common component of the cellular receptor complex for avian hepadnaviruses.


* Corresponding author. Mailing address: ZMBH, University of Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. Phone: 49 6221 546885. Fax: 49 6221 545893. E-mail: hshd{at}zmbh.uni-heidelberg.de.

dagger Present address: TAD Pharmazeutische Werke GmbH, 27472 Cuxhaven, Germany.

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


Journal of Virology, October 1998, p. 8089-8097, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.



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