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Journal of Virology, March 2000, p. 2203-2209, Vol. 74, No. 5
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

Klaus M. Breinerdagger and Heinz Schaller*

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.


* 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.

dagger Present address: K.M.B., Laboratorium für Biochemie, ETH Zürich, 8052 Zürich, Switzerland.


Journal of Virology, March 2000, p. 2203-2209, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.



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