Roles of lipid in HCV production

此前，我发现丙型肝炎病毒(丙型肝炎病毒)感染细胞中有脂滴积累。然而，脂滴堆积在丙型肝炎病毒增殖中的作用仍然不清楚。我们假设脂质代谢的失调调节对于允许丙型肝炎病毒的有效增殖是重要的。此外，我寻求另一种脂代谢的改变，这可能对丙型肝炎病毒的增殖也很重要。由于丙型肝炎病毒感染者血液中的丙型肝炎病毒与极低密度脂蛋白(VLDL)/低密度脂蛋白(LDL)等脂蛋白有关，我分析了脂蛋白合成对丙型肝炎病毒产生的影响。当微粒体甘油三酯转运蛋白(MTP)抑制剂阻断脂蛋白合成时，极低密度脂蛋白的产生受到抑制。同时，培养上清液中丙型肝炎病毒的分泌减少，这与载脂蛋白B的分泌减少相一致。这一结果表明丙型肝炎病毒的产生依赖于脂蛋白的生物合成。此外，丙型肝炎病毒的密度小于有序的球形RNA病毒，这一事实表明脂质成分与病毒颗粒有关。总而言之，我认为，丙型肝炎病毒劫持了脂质代谢以及有效增殖的脂质转移机制，这可能是推进肝功能衰竭的一个可能风险。

Previously, I discovered accumulation of lipid droplets in cells infected with hepatitis C virus (HCV). However, the roles of accumulation of lipid droplets in HCV proliferation remain elusive. We hypothesized that dys-regulation of lipid metabolism is important to allow efficient proliferation of HCV. Moreover, I sought another alteration of lipid metabolism which might be also important to HCV proliferation. Since it has been shown that HCV in blood from HCV infected individuals associates with lipoproteins such as very low density lipoprotein (VLDL)/low density lipoprotein (LDL), I analyzed effect of lipoprotein synthesis for HCV production. When lipoprotein synthesis was blocked by the inhibitor for microsomal triglyceride transfer protein (MTP), production of VLDL was suppressed. Simultaneously, secretion of HCV into culture medium was reduced, which coincided to reduction of secretion of apolipoprotein B. This result indicates that production of HCV depends on biosynthesis of lipoproteins. Moreover, the fact of that the density of HCV is smaller than ordinal spherical RNA viruses suggests association of lipid components with virus particles. Collectively, I propose that HCV hijacks lipid metabolism as well as lipid transfer mechanism for efficient proliferation, which may be a possible risk to advance liver failure.