Grant: Operating Grant

Hepatitis C virus (HCV) is a global health threat with substantial risk of end-stage liver disease causing death or a need for liver transplant. The majority of HCV circulating in blood of infected patients is in association with entities called lipoproteins that transport fat to be used by various tissues. Lipoproteins are classified by density attributed by their fat content. The most infectious populations of HCV are in the form of very low density lipoprotein (VLDL). VLDL is assembled only in liver and they get their cargo from fat stored in lipid droplets. Interestingly, agents that disrupt VLDL production also disrupt HCV production and lipid droplets appear to have an essential role in HCV production perhaps by acting as scaffolding for viral assembly. Fat retention in liver is a predominant clinical feature of HCV infection that enhances liver disease, and impaired VLDL assembly is a leading cause of lipid retention in liver. Our objective is to explore the possibility that decreased fat export with VLDL, causing fat retention, is essential for HCV production. The outcomes are expected to provide important insight regarding how infectious HCV is produced and why it causes liver disease.