FEBS Letters | |
The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine | |
Rowlands, David J.1  Evans, Stephen D.2  Griffin, Stephen D.C.1  Clarke, Dean S.1  Harris, Mark P.G.1  Beales, Lucy P.1  Jaeger, Joachim1  Worsfold, Oliver3  | |
[1] School of Biochemistry and Molecular Biology, University of Leeds, Division of Microbiology Old Medical School, Thoresby Place, Leeds LS2 9JT, UK;Department of Physics, University of Leeds, Leeds LS2 9JT, UK;Fujirebio Inc., 51 Komiya-cho, Hachioji-shi, Tokyo 192-0031, Japan | |
关键词: Hepatitis C virus; Flavivirus; p7; Viroporin; Amantadine; Antiviral therapy; | |
DOI : 10.1016/S0014-5793(02)03851-6 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
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.
【 授权许可】
Unknown
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