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Journal of Virology, October 1999, p. 8696-8702, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Carboxypeptidase D Is an Avian Hepatitis B Virus Receptor

Shuping Tong,dagger Jisu Li,dagger and Jack R. Wands*

Molecular Hepatology Laboratory, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts 02129

Received 15 April 1999/Accepted 28 June 1999

The receptor molecules for human and animal hepatitis B viruses have not been defined. Previous studies have described a 170 to 180 kDa molecule (p170 or gp180) that binds in vitro to the pre-S domain of the large envelope protein of duck hepatitis B virus (DHBV); cDNA cloning revealed the binding protein to be duck carboxypeptidase D (DCPD). In the present study, the DCPD cDNA was transfected into several nonpermissive human-, monkey-, and avian species-derived cell lines. Cells transfected with a plasmid encoding the full-length DCPD protein bound DHBV particles, whereas cells expressing truncated versions of DCPD protein that fail to bind the pre-S protein did not. The DHBV binding to DCPD-reconstituted cells was blocked by a monoclonal antibody that neutralizes DHBV infection of primary duck hepatocytes (PDH) and also by a pre-S peptide previously shown to inhibit DHBV infection of PDH. In addition to promoting virus binding, DCPD expression was associated with internalization of viral particles. The entry process was prevented by incubation of reconstituted cells with DHBV at 4°C and by the addition of energy-depleting agents known to block DHBV entry into PDH. These results demonstrated that DCPD is a DHBV receptor. However, the lack of complete viral replication in DCPD-reconstituted cells suggested that additional factors are required for postentry events in immortalized cell lines.


* Corresponding author. Present address: Liver Research Center, 55 Claverick St., 4th floor, Providence, RI 02903. Phone: (401) 444.2795. Fax: (401) 444.2939. E-mail: Jack_Wands_MD{at}Brown.edu.

dagger Present address: Liver Research Center, Rhode Island Hospital and Brown University School of Medicine, Providence, RI 02903.


Journal of Virology, October 1999, p. 8696-8702, Vol. 73, No. 10
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.



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