Roles of lipid in HCV production

先前，我发现在感染丙型肝炎病毒（HCV）的细胞中有脂滴积聚。然而，脂滴积聚在HCV增殖中的作用仍然是未知的。我们假设脂质代谢失调对HCV的有效增殖很重要。此外，我寻找另一种脂质代谢的改变，这可能对HCV增殖也很重要。由于已有研究表明HCV感染者血液中的HCV与极低密度脂蛋白(VLDL)/低密度脂蛋白（LDL）等脂蛋白相关，因此我分析了脂蛋白合成对HCV产生的影响。当微粒体甘油三酯转移蛋白（MTP）抑制剂阻断脂蛋白合成时，VLDL的产生受到抑制。同时，HCV在培养基中的分泌减少，这与载脂蛋白b的分泌减少相一致。这表明HCV的产生依赖于脂蛋白的生物合成。此外，HCV病毒的密度小于普通的球形RNA病毒，这表明脂质成分与病毒颗粒有关。综上所述，我认为HCV劫持了脂质代谢和脂质转移机制以实现有效增殖，这可能是推进肝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.