Requirement for Chloride Channel Function during the Hepatitis C Virus Life Cycle

Hepatocytes express an array of plasma membrane and intracellular ion channels, yet their role during the hepatitis C virus (HCV) life cycle remains largely undefined. Here, we show that HCV increases intracellular hepatic chloride (Cl(−)) influx that can be inhibited by selective Cl(−) channel blockers. Through pharmacological and small interfering RNA (siRNA)-mediated silencing, we demonstrate that Cl(−) channel inhibition is detrimental to HCV replication. This represents the first observation of the involvement of Cl(−) channels during the HCV life cycle.