MECHANISM OF BORNA-DISEASE VIRUS ENTRY INTO CELLS

We have investigated the entry pathway of Borna disease virus (BDV). V irus entry was assessed by detecting early viral replication and trans cription. Lysosomotropic agents (ammonium chloride, chloroquine, and a mantadine), as well as energy depletion, prevented BDV infection, indi cating that BDV enters host cells by endocytosis and requires an acidi c intracellular compartment to allow membrane fusion and initiate infe ction. Consistent with this hypothesis, we observed that BDV-infected cells form extensive syncytia upon low-pH treatment. Entry of envelope d viruses into animal cells usually requires the membrane-fusing activ ity of viral surface glycoproteins (GPs). BDV GP is expressed as two p roducts of 84 and 43 kDa (GP-84 and GP-43, respectively). We show here that only GP-43 is present at the surface of BDV-infected cells and t herefore is likely the viral polypeptide responsible for triggering fu sion events. We also present evidence that GP-43, which corresponds to the C terminus of GP-84, is generated by cleavage of GP-84 by the cel lular protease furin. Hence, we propose that BDV GP-84 is involved in attachment to the cell surface receptor whereas its furin-cleaved prod uct, GP-43, is involved in pH-dependent fusion after internalization o f the virion by endocytosis.