Unravelling the multiple roles of apolipoprotein E in the hepatitis C virus life cycle.

Abstract

Worldwide, about 3% of the population is infected with HCV, and chronic infection is associated with a risk of serious progressive liver disease. The recent introduction of direct-acting antiviral agents (DAAs) has considerably improved the treatment of chronic HCV infection, and most patients are now cured without major side effects.1 However, subgroups of patients difficult-to-treat and requiring additional therapeutic approaches will probably emerge. Furthermore, DAAs are very expensive, limiting their use in some countries.1 Thus, in the absence of prophylactic vaccines, improvements to our understanding of the mechanisms underlying virus assembly, maturation and secretion from the cell are required, to facilitate the development of new treatment options. In patients, HCV particles circulate as hybrid particles, known as lipoviroparticles (LVPs), combining components of both HCV and very low-density lipoprotein (VLDL).2 LVPs have a low density (<1.06 g/mL) and are highly infectious. Their maturation and release are tightly associated with VLDL synthesis, leading to cholesterol and triglyceride export from hepatocytes. Similar characteristics have been described for viruses produced in cell culture (HCVcc) by human Huh7.5 hepatoma cells.2 LVPs are rich in triacylglycerol and total cholesterol. They contain the viral RNA, capsid protein, envelope glycoproteins and apolipoproteins. They carry highly variable amounts of lipids and are therefore highly heterogeneous in size and density. LVPs have been shown to associate with apolipoprotein B and apolipoprotein E (ApoE).3 ApoE is a soluble and exchangeable apolipoprotein. It plays a critical role in VLDL assembly and is also involved in cellular lipid transport.2 The importance of ApoE for the life cycle of HCV has been confirmed by studies showing ApoE to be required for LVP production4 ,5 HCV infectivity being associated with the presence of ApoE in …