The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine

FEBS Letters

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