Amiodarone inhibits the entry and assembly steps of hepatitis C virus life cycle
Journal
Clinical Science
Journal Volume
125
Journal Issue
9
Pages
439-448
Date Issued
2013
Author(s)
Abstract
HCV (hepatitis C virus) infection affects an estimated 180 million people in the world's population. Adverse effects occur frequently with current standard treatment of interferon and ribavirin, while resistance of new direct anti-viral agents, NS3 protease inhibitors, is a major concern because of their single anti-HCV mechanism against the viral factor. New anti-viral agents are needed to resolve the problems. Amiodarone, an anti-arrhythmic drug, has recently been shown to inhibit HCV infection in vitro. The detailed mechanism has yet to be clarified. The aim of the present study was to elucidate the molecular mechanism of the inhibitory effect of amiodarone on HCV life cycle. The effect of amiodarone on HCV life cycle was investigated in Huh-7.5.1 cells with HCVcc (cell culture-derived HCV), HCVpp (HCV pseudoviral particles), sub-genomic replicons, IRES (internal ribosomal entry site)-mediated translation assay, and intracellular and extracellular infectivity assays. The administration of amiodarone appeared to inhibit HCV entry independent of genotypes, which was attributed to the down-regulation of CD81 receptor expression. The inhibitory effect of amiodarone also manifested in the HCV assembly step, via the suppression of MTP (microsomal triacylglycerol transfer protein) activity. Amiodarone revealed no effects on HCV replication and translation. With the host factor-targeting characteristics, amiodarone may be an attractive agent for the treatment of HCV infection. ? 2013 Biochemical Society.
Subjects
Amiodarone; CD81; Entry and assembly; Hepatitis C virus (HCV); Life cycle; Microsomal triacylglycerol transfer protein (MTP)
Other Subjects
amiodarone; CD81 antigen; triacylglycerol; article; controlled study; cytotoxicity; down regulation; drug mechanism; hepatitis C; Hepatitis C virus; human; human cell; internal ribosome entry site; life cycle; priority journal; replicon; virus entry; Amiodarone; Anti-Arrhythmia Agents; Antigens, CD81; Antiviral Agents; Cell Line, Tumor; Down-Regulation; Hepacivirus; Humans; Virus Replication
Type
journal article