Carboxypeptidase D is an avian hepatitis B virus receptor

The receptor molecules for human and animal hepatitis B viruses have not be en 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 pr otein of duck hepatitis B virus (DHBV); cDNA cloning revealed the binding p rotein 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 tru ncated 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 P DH. 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 degrees C and by the addi tion of energy-depleting agents known to block DHBV entry into PDH, These r esults demonstrated that DCPD is a DWBV receptor. However, the lack of comp lete viral replication in DCPD-reconstituted cells suggested that additiona l factors are required for postentry events in immortalized cell lines.