Roles of lipid in HCV production

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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.