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。在丙型肝炎病毒感染的肝脏中，肝脏代谢异常，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与病毒增殖有关的作用仍不清楚。我们分析了脂质及其代谢在丙型肝炎病毒产生中的作用，发现：(1)丙型肝炎病毒核心蛋白参与了感染细胞中脂滴的积累，(2)丙型肝炎病毒与脂蛋白成分(S)有关，脂蛋白E(Apo-E)对病毒的传染性起重要作用，(4)脂蛋白脂肪酶处理可能通过将Apo-E从病毒颗粒中解离而取消病毒的感染性，(5)丙型肝炎病毒的感染性受Apo-E亚型的影响，Apo-E3和-E4亚型表现为高传染性，Apo-E2低。我们还发现了一种新的脂蛋白受体，VLDLR，用于丙型肝炎病毒的进入。

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.