ANALYSIS OF VIRAL REPLICATION AND INFECTION MECHANISM OF THE DUCK HEPATITIS B VIRUS

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In an attempt to identify receptor candidates for DHBV, we have previously identified a glycoprotein of 180 kDa, which binds DHBV particles and Escherichia coli-derived GST-preS polypeptides. Sequence comparisons of gp18O cDNA with known sequences suggested that it represents the prototype of a new family of membrane bound carboxypeptidases. The primary sequence analysis indicates that CPDs consist of three luminal/extracellular carboxypeptidase B or H like domains (called A, B, and C), a hydrophobic transmembrane anchor and a highly conserved cytoplasmic tail. Domain C has been elucidated to have the DHBV preS-binding site. Now gp180, a Golgi-resident protein, is thought to be the cellular receptor for avian hepadnaviruses that mediates virus attachment and internalization into the host cell.All hepatitis B viruses (HBVs) display marked species specificity in their infection. We have examined the molecular basis for this narrow host range, using duck HBV (DHBV) and heron HBV (HHBV) as a model system. We have previously revealed that the preS domain of the large viral envelope protein determines host range in avian hepatitis B viruses, by pseudotyping of HHBV env with DHBV/HHBV chimeric envelope proteins. To further map the determinant in the DHBV preS region, we have made DHBV/HHBV chimeric envelope proteins (HDC 6-12). The replacement of as few as 15 amino acids of the preS domain of the HHBV L protein by their counterparts is sufficient to permit infection of duck hepatocytes. This domain is located between amino acid 22 and 37 in the DHBV preS sequence, which is outside of and more amino terminal domain of duck carboxypeptidase D (dCPD) binding sites (amino acid 43-108).These results suggest that dCPD could not be the sole determinant of viral entry, and this domain might be responsible for the binding of the putative second receptor in hepadnaviral infection.