Fumitake Amemiya,
Shinya Maekawa,
Yoshie Itakura,
Asuka Kanayama,
Akira Matsui,
Shinichi Takano,
Tatsuya Yamaguchi,
Jun Itakura,
Takatoshi Kitamura,
Taisuke Inoue,
Minoru Sakamoto,
Kozue Yamauchi,
Shunichi Okada,
Atsuya Yamashita,
Naoya Sakamoto, Masahiko Itoh,
Nobuyuki Enomoto
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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.
The Journal of Infectious Diseases 03/2008; 197(3):361-70. · 6.41 Impact Factor
