Mechanism of Borna disease virus entry into cells.
We have investigated the entry pathway of Borna disease virus (BDV). Virus entry was assessed by detecting early viral replication and transcription. Lysosomotropic agents (ammonium chloride, chloroquine, and amantadine), as well as energy depletion, prevented BDV infection, indicating that BDV enters host cells by endocytosis and requires an acidic intracellular compartment to allow membrane fusion and initiate infection. Consistent with this hypothesis, we observed that BDV-infected cells form extensive syncytia upon low-pH treatment. Entry of enveloped viruses into animal cells usually requires the membrane-fusing activity of viral surface glycoproteins (GPs). BDV GP is expressed as two products 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 therefore is likely the viral polypeptide responsible for triggering fusion 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 cellular protease furin. Hence, we propose that BDV GP-84 is involved in attachment to the cell surface receptor whereas its furin-cleaved product, GP-43, is involved in pH-dependent fusion after internalization of the virion by endocytosis.
Gonzalez-Dunia
D
D
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Cubitt
B
B
de la Torre
J C
JC
D000547:Amantadine / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001891:Borna disease virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D004705:Endocytosis; D015726:Giant Cells; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000187:drug effects; D008561:Membrane Fusion; D051381:Rats; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D014764:Viral Proteins; D000643:Ammonium Chloride; D002738:Chloroquine; D000547:Amantadine