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丙型肝炎病毒核心蛋白、脂滴与脂肪变性

Hepatitis C virus core protein, lipid droplets and steatosis.

作者信息

Roingeard P, Hourioux C

机构信息

INSERM ERI 19, Université François Rabelais & CHRU de Tours, Tours, France.

出版信息

J Viral Hepat. 2008 Mar;15(3):157-64. doi: 10.1111/j.1365-2893.2007.00953.x. Epub 2007 Dec 17.

Abstract

Lipid droplets are intracellular organelles involved not only in lipid storage but also in cell signalling and the regulation of intracellular vesicular trafficking. Recent basic studies have suggested that interactions between hepatitis C virus (HCV) core protein and lipid droplets are required for the HCV infection cycle. In infected cells, the HCV core protein is associated with the surface of lipid droplets and the endoplasmic reticulum membranes closely surrounding these droplets, and its self-assembly drives virion budding. This interaction also seems to be directly linked to a virus-induced steatosis, which involves the deposition of triglycerides in the liver and contributes to the progression of fibrosis in patients with chronic hepatitis C. Many clinical studies have reported that virus-induced steatosis is significantly more severe with HCV genotype 3 than with other genotypes, and this phenomenon has been modelled in recent basic studies based on the production of HCV core proteins of various genotypes in vitro. The association of HCV core protein with lipid droplets seems to play a central role in HCV pathogenesis and morphogenesis, suggesting that virus-induced steatosis may be essential for the viral life cycle.

摘要

脂滴是细胞内的细胞器,不仅参与脂质储存,还参与细胞信号传导和细胞内囊泡运输的调节。最近的基础研究表明,丙型肝炎病毒(HCV)核心蛋白与脂滴之间的相互作用是HCV感染周期所必需的。在受感染的细胞中,HCV核心蛋白与脂滴表面以及紧密围绕这些脂滴的内质网膜相关联,其自组装驱动病毒粒子出芽。这种相互作用似乎也与病毒诱导的脂肪变性直接相关,脂肪变性涉及肝脏中甘油三酯的沉积,并有助于慢性丙型肝炎患者纤维化的进展。许多临床研究报告称,HCV 3型病毒诱导的脂肪变性比其他基因型严重得多,最近的基础研究已基于体外产生的各种基因型的HCV核心蛋白对此现象进行了模拟。HCV核心蛋白与脂滴的关联似乎在HCV发病机制和形态发生中起核心作用,这表明病毒诱导的脂肪变性可能对病毒生命周期至关重要。

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