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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,
Ursula
Klingmüller,
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.

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

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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