Article

Targeting lipid metabolism in the treatment of hepatitis C virus infection.

First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Chuo, Japan.
The Journal of Infectious Diseases (impact factor: 6.41). 03/2008; 197(3):361-70. DOI:10.1086/525287 pp.361-70
Source: PubMed

ABSTRACT Recently, microdomains of organelle membranes rich in sphingomyelin and cholesterol (called "lipid rafts") have been considered to act as a scaffold for the hepatitis C virus (HCV) replication complex. Using the HCV cell culture system, we investigated the effect of myriocin, a sphingomyelin synthesis inhibitor, on HCV replication. We also investigated the combined effect of myriocin with interferon (IFN) and myriocin with simvastatin. Myriocin suppressed replication of both a genotype 1b subgenomic HCV replicon (Huh7/Rep-Feo) and genotype 2a infectious HCV (JFH-1 HCV) in a dose-dependent manner (for subgenomic HCV-1b, maximum of 79% at 1000 nmol/L; for genomic HCV-2a, maximum of 40% at 1000 nmol/L). Combination treatment with myriocin and IFN or myriocin and simvastatin attenuated HCV RNA replication synergistically in Huh7/Rep-Feo cells. Our data demonstrate that the sphingomyelin synthesis inhibitor strongly suppresses replication of both the subgenomic HCV-1b replicon and the JFH-1 strain of genotype 2a infectious HCV, indicating that lipid metabolism could be a novel target for HCV therapy.

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Keywords

dose-dependent manner
 
genomic HCV-2a
 
genotype 1b subgenomic HCV replicon
 
genotype 2a infectious HCV
 
HCV cell culture system
 
HCV replication
 
HCV therapy
 
hepatitis C virus
 
Huh7/Rep-Feo cells
 
JFH-1 HCV
 
JFH-1 strain
 
lipid metabolism
 
lipid rafts"
 
Myriocin suppressed replication
 
novel target
 
organelle membranes rich
 
simvastatin attenuated HCV RNA replication synergistically
 
sphingomyelin synthesis inhibitor
 
subgenomic HCV-1b
 
subgenomic HCV-1b replicon