Critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection
Critical role of virion-associated cholesterol and sphingolipid in hepatitis C virus infection
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DOI：
10.1128/jvi.02530-07
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发表时间：
2008-06-01
影响因子：
5.4
通讯作者：
Suzuki, Tetsuro
中科院分区：
文献类型：
--
作者：
Aizaki, Hideki;Morikawa, Kenichi;Suzuki, Tetsuro
在这项研究中，我们建立了胆固醇和鞘脂与丙型肝炎病毒（HCV）颗粒是重要的病毒粒子的成熟和感染性。在最近开发的培养系统，使研究HCV的完整的生命周期，成熟的病毒体富含胆固醇，通过胆固醇的摩尔比，磷脂在病毒体和细胞膜进行评估。胆固醇从病毒或水解病毒粒子相关的鞘磷脂几乎完全废除HCV的感染性。补充胆固醇耗尽的病毒与外源性胆固醇增强感染性的水平相当于未经处理的控制。胆固醇耗尽或鞘磷脂水解病毒有明显缺陷的内化，但没有观察到对细胞附着的影响。HCV结构蛋白的重要部分分配到细胞洗涤剂抗性，脂筏样膜。结合鞘脂生物合成途径的抑制剂阻断病毒体的产生，但不是RNA的积累，在JFH-1分离，我们的研究结果表明，改变HCV颗粒的脂质组成可能是一个有用的方法，在抗HCV治疗的设计。
In this study, we establish that cholesterol and sphingolipid associated with hepatitis C virus (HCV) particles are important for virion maturation and infectivity. In a recently developed culture system enabling study of the complete life cycle of HCV, mature virions were enriched with cholesterol as assessed by the molar ratio of cholesterol to phospholipid in virion and cell membranes. Depletion of cholesterol from the virus or hydrolysis of virion-associated sphingomyelin almost completely abolished HCV infectivity. Supplementation of cholesterol-depleted virus with exogenous cholesterol enhanced infectivity to a level equivalent to that of the untreated control. Cholesterol-depleted or sphingomyelin-hydrolyzed virus had markedly defective internalization, but no influence on cell attachment was observed. Significant portions of HCV structural proteins partitioned into cellular detergent-resistant, lipid-raft-like membranes. Combined with the observation that inhibitors of the sphingolipid biosynthetic pathway block virion production, but not RNA accumulation, in a JFH-1 isolate, our findings suggest that alteration of the lipid composition of HCV particles might be a useful approach in the design of anti-HCV therapy.