The p7 protein of hepatitis C virus forms an ion channel that is blocked by the antiviral drug, Amantadine.
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.
Griffin
Stephen D C
SD
School of Biochemistry and Molecular Biology, University of Leeds, Division of Microbiology Old Medical School, Thoresby Place, Leeds LS2 9JT, UK.
Beales
Lucy P
LP
Clarke
Dean S
DS
Worsfold
Oliver
O
Evans
Stephen D
SD
Jaeger
Joachim
J
Harris
Mark P G
MP
Rowlands
David J
DJ
D000547:Amantadine / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry; D008567:Membranes, Artificial; D008854:Microscopy, Electron; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D000086082:Viroporin Proteins
D000547:Amantadine; D000998:Antiviral Agents; D007473:Ion Channels; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins