Cellular receptor traffic is essential for productive duck hepatitis B virus infection

We have investigated the mechanism of duck hepatitis B virus (DHBV) entry i nto susceptible primary duck hepatocytes (PDHs), using mutants of carboxype ptidase D (gp180), a transmembrane protein shown to act as the primary cell ular receptor for avian hepatitis B virus uptake, The variant proteins were abundantly produced from recombinant adenoviruses and tested for the poten tial to functionally outcompete the endogenous wild-type receptor, Overexpr ession of wild-type gp180 significantly enhanced the efficiency of DHBV inf ection in PDHs but did not affect ongoing DHBV replication, an observation further supporting gp180 receptor function. A gp180 mutant deficient for en docytosis abolished DHBV infection, indicating endocytosis to be the route of hepadnaviral entry, With further gp180 variants, carrying mutations in t he cytoplasmic domain and characterized by an accelerated turnover, the abi lity 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 endol ysosomal compartment. Based on these data, we propose a model in which a di stinct intracellular DHBV traffic to the endosome, but not beyond, is a pre requisite for completion of viral entry, i.e., for fusion and capsid releas e, Furthermore, the deletion of the two enzymatically active carboxypeptida se domains of gp180 did not lead to a loss of receptor function.