The hepatitis C virus p7 protein forms an ion channel that is inhibited by long-alkyl-chain iminosugar derivatives

Abstract

We show that hepatitis C virus (HCV) p7 protein forms ion channels in black lipid membranes. HCV p7 ion channels are inhibited by long-alkyl-chain iminosugar derivatives, which have antiviral activity against the HCV surrogate bovine viral diarrhea virus. HCV p7 presents a potential target for antiviral therapy.

Figure 1

(A) Channel recordings of synthetic HCV p7 inserted into a BLM. Channel activity is shown for ±100 mV. The closed state is shown as a solid line. Openings are deviations from this line. Solutions are the same in cis and trans: 0.5 M KCl/5 mM Hepes/1 mM CaCl₂, pH 7.4. p7 is added on the trans side to a final concentration of ≈50 μM. (B) Current trace recorded after ≈30 min of data collection. Scale bars are 10 s and 100 pA.

Figure 2

Effect of short- and long-alkyl-chain iminosugar derivatives on p7 channel signals in BLM. The closed state is shown as a solid line. Openings are deviations from this line. Scale bars are 15 s and 40 pA. Solutions are the same in cis and trans: 0.5 M KCl/5 mM Hepes/1 mM CaCl₂, pH 7.4. p7 is added on the trans side to a final concentration of ≈50 μM. Compounds were added at a constant holding potential of +100 mV on the cis side to the final concentrations indicated at the left side of each recording.

Figure 3

Effect of N-7-oxanonyl-6-deoxy-DGJ on p7 channel signals in BLM. The closed state is shown as a solid line. Openings are deviations from this line. Scale bars are 20 s and 400 pA. Solutions are the same in cis and trans: 0.5 M KCl/5 mM Hepes/1 mM CaCl₂, pH 7.4. p7 is added on the trans side to a final concentration of ≈50 μM. N-7-oxanonyl-6-deoxy-DGJ was added at a constant holding potential of +130 mV on the trans side to the final concentrations indicated at the left side of each recording.