Research Institute, Chiba Institute of Technology, Tsudanuma, Narashino, Chiba 275-0016, Japan.
Curr Opin Virol. 2011 Jul;1(1):19-26. doi: 10.1016/j.coviro.2011.05.017. Epub 2011 Jun 12.
Many chronic hepatitis patients with hepatitis C virus (HCV) are observed to have a degree of steatosis which is a factor in the progression of liver diseases. Transgenic mice expressing HCV core protein develop liver steatosis before the onset of hepatocellular carcinoma, suggesting active involvement of HCV in the de-regulation of lipid metabolism in host cells. However, the role of lipid metabolism in HCV life cycle has not been fully understood until the establishment of in vitro HCV infection and replication system. In this review we focus on HCV production with regard to modification of lipid metabolism observed in an in vitro HCV infection and replication system. The importance of lipid droplet to HCV production has been recognized, possibly at the stage of virus assembly, although the precise mechanism of lipid droplet for virus production remains elusive. Association of lipoprotein with HCV in circulating blood in chronic hepatitis C patients is observed. In fact, HCV released from culture medium is also associated with lipoprotein. The fact that treatment of HCV fraction with lipoprotein lipase (LPL) abolished infectivity indicates the essential role of lipoprotein's association with virus particle in the virus life cycle. In particular, apolipoprotein E (ApoE), a component of lipoprotein associated with HCV plays a pivotal role in HCV infectivity by functioning as a virus ligand to lipoprotein receptor that also functions as HCV receptor. These results strongly suggest the direct involvement of lipid metabolism in the regulation of the HCV life cycle.
许多慢性丙型肝炎病毒（HCV）患者存在一定程度的脂肪变性，这是肝病进展的一个因素。表达 HCV 核心蛋白的转基因小鼠在肝癌发生前就出现了肝脂肪变性，这表明 HCV 积极参与了宿主细胞脂质代谢的失调。然而，直到建立体外 HCV 感染和复制系统，脂质代谢在 HCV 生命周期中的作用才被充分理解。在这篇综述中，我们重点关注体外 HCV 感染和复制系统中观察到的脂质代谢改变与 HCV 产生的关系。脂滴在 HCV 产生中的重要性已经得到认可，可能在病毒组装阶段，但脂滴在病毒产生中的精确机制仍不清楚。在慢性丙型肝炎患者的循环血液中观察到脂蛋白与 HCV 的关联。事实上，从培养基中释放的 HCV 也与脂蛋白有关。用脂蛋白脂肪酶（LPL）处理 HCV 馏分可消除感染性，这一事实表明脂蛋白与病毒颗粒的关联在病毒生命周期中起着至关重要的作用。特别是，载脂蛋白 E（ApoE）是与 HCV 相关的脂蛋白的一个组成部分，通过作为脂蛋白受体的病毒配体发挥作用，而脂蛋白受体也作为 HCV 受体发挥作用，从而在 HCV 感染性中发挥关键作用。这些结果强烈表明脂质代谢的直接参与调节 HCV 生命周期。
