Targeting lipid metabolism in the treatment of hepatitis C virus infection
Targeting lipid metabolism in the treatment of hepatitis C virus infection
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DOI：
10.1086/525287
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发表时间：
2008-02-01
影响因子：
6.4
通讯作者：
Enomoto, Nobuyuki
中科院分区：
文献类型：
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作者：
Amemiya, Fumitake;Maekawa, Shinya;Enomoto, Nobuyuki
最近，富含鞘磷脂和胆固醇的细胞器膜微区（称为“脂筏”）被认为是丙型肝炎病毒（HCV）复制复合物的支架。使用HCV细胞培养系统，我们研究了多球壳菌素，鞘磷脂合成抑制剂，对HCV复制的影响。我们还研究了多球菌素与干扰素（IFN）和多球菌素与辛伐他汀的联合作用。多孢菌素以剂量依赖性方式抑制基因型1b亚基因组HCV复制子（Huh 7/Rep-Feo）和基因型2a感染性HCV（JFH-1 HCV）的复制（对于亚基因组HCV-1b，在1000 nmol/L时最大值为79%;对于基因组HCV-2a，在1000 nmol/L时最大值为40%）。在Huh 7/Rep-Feo细胞中，用多球菌素和IFN或多球菌素和辛伐他汀联合治疗协同减弱HCV RNA复制。我们的数据表明，鞘磷脂合成抑制剂强烈抑制复制的亚基因组HCV-1b复制子和JFH-1株基因型2a感染性HCV，表明脂质代谢可能是一个新的目标HCV治疗。
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.