Avian hepatitis B virus infection is initiated by the interaction of a distinct pre-S subdomain with the cellular receptor gp180.
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.
Urban
S
S
Zentrum für Molekulare Biologie, Universität Heidelberg, 69120 Heidelberg, Germany.
Breiner
K M
KM
Fehler
F
F
Klingmüller
U
U
Schaller
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D002268:Carboxypeptidases / Q000737:chemistry / Q000378:metabolism*; D018347:Hepadnaviridae Infections / Q000378:metabolism* / Q000821:virology; D015611:Hepatitis B Virus, Duck / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011506:Proteins; D011994:Recombinant Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000378:metabolism*
D008562:Membrane Glycoproteins; C077433:Pre-S protein, Duck hepatitis B virus; D011506:Proteins; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D002268:Carboxypeptidases; C094315:metallocarboxypeptidase D