Source
Institute of Virology, Technische Universität München / Helmholtz
Zentrum München, Trogerstrasse, 30, 81675 Munich, Germany.
Abstract
Current treatment of chronic Hepatitis B virus (HBV) infection mainly
targets viral replication in hepatocytes and leads to curing only in
exceptional cases. Despite their potential to improve therapeutic
success, no drugs interfering with early infection steps of the
hepatotropic pathogen HBV are available to date. Recently, entry of the
Hepatitis C virus (HCV) has been shown to occur along hepatic
cholesterol uptake pathways and ezetimibe, a drug which blocks this
lipid transport, has been shown to inhibit HCV infection. We here
investigated the effect of ezetimibe on HBV infection using
differentiated HepaRG-cells as a cell-culture infection model. Treatment
with ezetimibe inhibited establishment of intrahepatic cccDNA and
expression of viral replication markers when cells were infected with
HBV virions, while we observed no effect when the HBV viral genome was
transduced via an adenoviral vector. Our data suggest that modulating
hepatic cholesterol uptake by ezetimibe inhibits early HBV infection and
that ezetimibe sensitive lipid transport pathways represent new targets
for antiviral therapy in HBV infection.