Cation-selective ion channels formed by p7 of hepatitis C virus are blocked by hexamethylene amiloride.
A 63 residue peptide, p7, encoded by hepatitis C virus was synthesised and tested for ion channel activity in lipid bilayer membranes. Ion channels formed by p7 had a variable conductance: some channels had conductances as low as 14 pS. The reversal potential of currents flowing through the channels formed by p7 showed that they were permeable to potassium and sodium ions and less permeable to calcium ions. Addition of Ca(2+) to solutions made channels formed by p7 less potassium- or sodium-selective. Hexamethylene amiloride, a drug previously shown to block ion channels formed by Vpu encoded by HIV-1, blocked channels formed by p7. In view of the increasing number of peptides encoded by viruses that have been shown to form ion channels, it is suggested that ion channels may play an important role in the life cycle of many viruses and that drugs that block these channels may prove to be useful antiviral agents.
Premkumar
A
A
John Curtin School of Medical Research, Australian National University, GPO Box 334, Canberra, ACT 2601, Australia.
Wilson
L
L
Ewart
G D
GD
Gage
P W
PW
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D007473:Ion Channels / Q000096:biosynthesis* / Q000187:drug effects; D008051:Lipid Bilayers; D008564:Membrane Potentials / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014764:Viral Proteins / Q000737:chemistry / Q000494:pharmacology*; D000086082:Viroporin Proteins
D000584:Amiloride; D007473:Ion Channels; D008051:Lipid Bilayers; D010446:Peptide Fragments; D014764:Viral Proteins; C088369:p7 protein, Hepatitis C virus; D000086082:Viroporin Proteins; C057360:5-(N,N-hexamethylene)amiloride