title: Amantadine inhibits the function of an ion channel encoded by GB virus B, but fails to inhibit virus replication.
abstract: A chemically synthesized peptide representing the C-terminal subunit (p13-C) of the p13 protein of GB virus B (GBV-B), the most closely related virus to hepatitis C virus (HCV) showed ion channel activity in artificial lipid bilayers. The channels had a variable conductance and were more permeable to potassium ions than to chloride ions. Amantadine but not hexamethylene amiloride (HMA) inhibited the ion channel function of p13-C in the lipid membranes. However, neither agent was able to inhibit the replication and secretion of GBV-B from virus-infected cultured marmoset hepatocytes, which were harvested from a marmoset that was infected in vivo or inhibit replication after in vitro infection of naive hepatocytes. These data suggest that the GBV-B ion channel, contrary to the data derived from the lipid membranes, is either resistant to amantadine or that virus replication and secretion are independent of ion channel function. As the p7 protein of HCV also has ion channel activity that is apparently resistant to amantadine in vivo, the former possibility is most likely. Ion channels are likely to have an important role in the life cycle of many viruses and compounds that block these channels may prove to be useful antiviral agents.
authors.affiliation: John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia.
authors.forename: Anita
authors.initials: A
authors.lastname: Premkumar
authors.forename: Xuebin
authors.initials: X
authors.lastname: Dong
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Haqshenas
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gage
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Gowans
mesh_terms: D000547:Amantadine / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002144:Callithrix; D002478:Cells, Cultured; D018178:Flaviviridae Infections / Q000821:virology; D029406:GB virus B / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006524:Hepatitis, Viral, Animal / Q000821:virology; D022781:Hepatocytes / Q000821:virology; D007473:Ion Channels / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D008051:Lipid Bilayers; D008969:Molecular Sequence Data; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D014764:Viral Proteins; D000547:Amantadine