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Journal of Virology, March 2000, p. 2203-2209, Vol. 74, No. 5
Microbiology and Zentrum für Molekulare
Biologie, Universität Heidelberg, 69120 Heidelberg, Germany
Received 23 August 1999/Accepted 30 November 1999
We have investigated the mechanism of duck hepatitis B virus (DHBV)
entry into susceptible primary duck hepatocytes (PDHs), using mutants
of carboxypeptidase D (gp180), a transmembrane protein shown to act as
the primary cellular receptor for avian hepatitis B virus uptake. The
variant proteins were abundantly produced from recombinant adenoviruses
and tested for the potential to functionally outcompete the endogenous
wild-type receptor. Overexpression of wild-type gp180 significantly
enhanced the efficiency of DHBV infection in PDHs but did not affect
ongoing DHBV replication, an observation further supporting gp180
receptor function. A gp180 mutant deficient for endocytosis abolished
DHBV infection, indicating endocytosis to be the route of hepadnaviral
entry. With further gp180 variants, carrying mutations in the
cytoplasmic domain and characterized by an accelerated turnover, the
ability of gp180 to function as a DHBV receptor was found to depend on
a wild-type-like sorting phenotype which largely avoids transport
toward the endolysosomal compartment. Based on these data, we propose a
model in which a distinct intracellular DHBV traffic to the endosome,
but not beyond, is a prerequisite for completion of viral entry, i.e., for fusion and capsid release. Furthermore, the deletion of the two
enzymatically active carboxypeptidase domains of gp180 did not lead to
a loss of receptor function.
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Cellular Receptor Traffic Is Essential for
Productive Duck Hepatitis B Virus Infection
and
*
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.
Present address: K.M.B., Laboratorium für Biochemie, ETH
Zürich, 8052 Zürich, Switzerland.
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