Griffin Stephen D C, Beales Lucy P, Clarke Dean S, Worsfold Oliver, Evans Stephen D, Jaeger Joachim, Harris Mark P G, Rowlands David J
School of Biochemistry and Molecular Biology, University of Leeds, Division of Microbiology Old Medical School, Thoresby Place, Leeds LS2 9JT, UK.
FEBS Lett. 2003 Jan 30;535(1-3):34-8. doi: 10.1016/s0014-5793(02)03851-6.
Hepatitis C virus (HCV) cannot be grown in vitro, making biochemical identification of new drug targets especially important. HCV p7 is a small hydrophobic protein of unknown function, yet necessary for particle infectivity in related viruses [Harada, T. et al., (2000) J. Virol. 74, 9498-9506]. We show that p7 can be cross-linked in vivo as hexamers. Escherichia coli expressed p7 fusion proteins also form hexamers in vitro. These and HIS-tagged p7 function as calcium ion channels in black lipid membranes. This activity is abrogated by Amantadine, a compound that inhibits ion channels of influenza [Hay, A.J. et al. (1985) EMBO J. 4, 3021-3024; Duff, K.C. and Ashley, R.H. (1992) Virology 190, 485-489] and has recently been shown to be active in combination with current HCV therapies.
丙型肝炎病毒（HCV）无法在体外培养，这使得新药靶点的生化鉴定尤为重要。HCV p7是一种功能未知的小疏水蛋白，但对于相关病毒的颗粒感染性是必需的[原田，T.等人，（2000年）《病毒学杂志》74卷，9498 - 9506页]。我们发现p7在体内可交联形成六聚体。大肠杆菌表达的p7融合蛋白在体外也能形成六聚体。这些以及带有组氨酸标签的p7在黑色脂质膜中作为钙离子通道发挥作用。这种活性可被金刚烷胺消除，金刚烷胺是一种抑制流感病毒离子通道的化合物[海，A.J.等人（1985年）《欧洲分子生物学组织杂志》4卷，3021 - 3024页；达夫，K.C.和阿什利，R.H.（1992年）《病毒学》190卷，485 - 489页]，并且最近已证明它与当前的HCV疗法联合使用时具有活性。
