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Deciphering the role of lipid droplets in Hepatitis C virus replication

破译脂滴在丙型肝炎病毒复制中的作用

基本信息

批准号：
248680339
负责人：
Professorin Dr. Eva Herker
金额：
--
依托单位：
Institut für Virologie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/248680339?language=en
关键词：
Deciphering role lipid droplets Hepatitis

项目摘要

Hepatitis C virus (HCV) infection affects approximately 3% of the world's population and is one of the leading causes of liver-related morbidity and mortality. HCV infection as well as replication of the virus is closely tied to the lipid metabolism of infected hepatocytes. About half of all individuals chronically infected with HCV develop fatty liver disease, a condition characterized by the massive accumulation of lipid droplets in infected cells. Intriguingly, lipid droplets also emerged as crucial organelles for HCV infection, particularly for assembly of viral progeny. However, why the virus requires lipid droplets for replication as well as the mechanistic details of the late steps of HCV replication remain ill defined. Our goal is to elucidate in molecular detail the role of lipid droplets in HCV infection and pathogenesis. We have previously shown that host proteins involved in lipid droplet biogenesis and function serve as key regulators of viral replication. We then compared lipid droplet-associated proteins in HCV-infected versus control cells and identified candidate proteins that may serve as host-dependency or -restriction factors that will be now studied in molecular detail. Functional annotation suggests that HCV infection causes a disconnection of lipid droplets from metabolic function and/or regulation. The experiments proposed here will decipher molecular mechanisms and temporal/spatial coordination of HCV assembly, maturation, and egress. In addition they will further elucidate the function of lipid droplets in HCV replication and pathogenesis.

丙型肝炎病毒（HCV）感染影响约3%的世界人口，并且是肝脏相关发病率和死亡率的主要原因之一。HCV感染以及病毒复制与受感染肝细胞的脂质代谢密切相关。大约一半的慢性HCV感染者会发展成脂肪肝，这种疾病的特征是脂滴在受感染的细胞中大量积聚。有趣的是，脂滴也成为HCV感染的关键细胞器，特别是对于病毒后代的组装。然而，为什么病毒需要脂滴复制以及HCV复制后期步骤的机制细节仍然不清楚。我们的目标是从分子水平详细阐明脂滴在HCV感染和发病机制中的作用。我们以前已经表明，宿主蛋白质参与脂滴的生物发生和功能作为病毒复制的关键调节因子。然后，我们比较了HCV感染细胞与对照细胞中的脂滴相关蛋白，并确定了可能作为宿主依赖性或限制性因子的候选蛋白质，这些蛋白质将在分子水平上进行详细研究。功能注释表明HCV感染导致脂滴与代谢功能和/或调节断开。这里提出的实验将破译HCV组装、成熟和排出的分子机制和时间/空间协调。此外，他们将进一步阐明脂滴在HCV复制和发病机制中的功能。