Targeting lipid metabolism in the treatment of hepatitis C virus infection

被引：53

作者：

Amemiya, Fumitake ^{[1
]}

Maekawa, Shinya ^{[1
]}

Itakura, Yoshie ^{[1
]}

Kanayama, Asuka ^{[1
]}

Matsui, Akira ^{[1
]}

Takano, Shinichi ^{[1
]}

Yamaguchi, Tatsuya ^{[1
]}

Itakura, Jun ^{[1
]}

Kitamura, Takatoshi ^{[1
]}

Inoue, Taisuke ^{[1
]}

Sakamoto, Minoru ^{[1
]}

Yamauchi, Kozue ^{[1
]}

Okada, Shunichi ^{[1
]}

Yamashita, Atsuya ^{[2
]}

Sakamoto, Naoya ^{[3
]}

Itoh, Masahiko ^{[2
]}

Enomoto, Nobuyuki ^{[1
]}

机构：

[1] Univ Yamanashi, Dept Internal Med 1, Fac Med, Yamanashi 4093898, Japan

[2] Univ Yamanashi, Dept Microbiol, Fac Med, Yamanashi 4093898, Japan

[3] Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Tokyo, Japan

来源：

JOURNAL OF INFECTIOUS DISEASES | 2008年 / 197卷 / 03期

关键词：

D O I：

10.1086/525287

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：361 / 370

页数：10

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