Premkumar Anita, Dong Xuebin, Haqshenas Gholamreza, Gage Peter W, Gowans Eric J
John Curtin School of Medical Research, Australian National University, Canberra ACT, Australia.
Antivir Ther. 2006;11(3):289-95.
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.
一种化学合成的肽段，它代表了丙型肝炎病毒（HCV）最密切相关病毒——GB病毒B（GBV - B）的p13蛋白的C末端亚基（p13 - C），在人工脂质双分子层中显示出离子通道活性。这些通道具有可变的电导率，对钾离子的通透性比对氯离子的通透性更高。金刚烷胺而非六甲铵（HMA）抑制了脂质膜中p13 - C的离子通道功能。然而，这两种药物都不能抑制从体内感染的狨猴收获的病毒感染培养狨猴肝细胞中GBV - B的复制和分泌，也不能抑制体外感染未感染肝细胞后的复制。这些数据表明，与从脂质膜获得的数据相反，GBV - B离子通道要么对金刚烷胺有抗性，要么病毒复制和分泌与离子通道功能无关。由于HCV的p7蛋白在体内也具有明显对金刚烷胺有抗性的离子通道活性，前一种可能性最大。离子通道可能在许多病毒的生命周期中起重要作用，阻断这些通道的化合物可能被证明是有用的抗病毒药物。
