The role of lipid metabolism on HCV proliferation

慢性丙型肝炎患者常发展为脂肪性肝炎。在HCV感染的肝脏中，肝脏代谢异常高，通常是由肝脏代谢激活引起的，但这种高代谢激活在细胞中对病毒增殖的作用尚不清楚。我们分析了脂质及其代谢在HCV产生中的作用，发现；(1) HCV核心蛋白参与了感染细胞内脂滴的积累，(2)HCV与对病毒感染性有重要影响的脂蛋白组分相关，(3)特别是载脂蛋白E （Apo-E）在病毒的感染性中起重要作用，(4)脂蛋白脂酶处理可能通过将载脂蛋白E与病毒颗粒分离来消除病毒的感染性，(5)HCV的感染性受载脂蛋白E亚型的影响。Apo-E3和-E4亚型具有高传染性，而Apo-E2亚型具有低传染性。我们还发现了一种新的脂蛋白受体，VLDLR，用于HCV进入。

Patients with chronic hepatitis C often develop steato-hepatitis. Abnormality of liver metabolism, often caused by activation of liver metabolism, in HCV infected liver is high, but roles of such the high metabolic activation in the cells in regards to virus proliferation remains elusive. We analyzed the role of lipid as well as its metabolism on HCV production and found; (1) HCV core protein is involved in accumulation of lipid droplet in the infected cells, (2) HCV associates with lipoprotein component(s) which is important for virus infectivity, (3) in particular, apolipoprotein E (Apo-E) plays an important roles in virus infectivity, (4) lipoprotein lipase treatment abolished virus infectivity possibly by dissociation of Apo-E from virus particle, (5) HCV infectivity is influenced by Apo-E isoforms; Apo-E3 and –E4 isoforms show high infectivity and Apo-E2 low. We also found a new lipoprotein receptor, VLDLR, for HCV entry.