Chronic hepatitis C virus infection and lipoprotein metabolism

Abstract

Hepatitis C virus (HCV) is a hepatotrophic virus and a major cause of chronic liver disease, including hepatocellular carcinoma, worldwide. The life cycle of HCV is closely associated with the metabolism of lipids and lipoproteins. The main function of lipoproteins is transporting lipids throughout the body. Triglycerides, free cholesterol, cholesteryl esters, and phospholipids are the major components of the transported lipids. The pathway of HCV assembly and secretion is closely linked to lipoprotein production and secretion, and the infectivity of HCV particles largely depends on the interaction of lipoproteins. Moreover, HCV entry into hepatocytes is strongly influenced by lipoproteins. The key lipoprotein molecules mediating these interactions are apolipoproteins. Apolipoproteins are amphipathic proteins on the surface of a lipoprotein particle, which help stabilize lipoprotein structure. They perform a key role in lipoprotein metabolism by serving as receptor ligands, enzyme co-factors, and lipid transport carriers. Understanding the association between the life cycle of HCV and lipoprotein metabolism is important because each step of the life cycle of HCV that is associated with lipoprotein metabolism is a potential target for anti-HCV therapy. In this article, we first concisely review the nature of lipoprotein and its metabolism to better understand the complicated interaction of HCV with lipoprotein. Then, we review the outline of the processes of HCV assembly, secretion, and entry into hepatocytes, focusing on the association with lipoproteins. Finally, we discuss the clinical aspects of disturbed lipid/lipoprotein metabolism and the significance of dyslipoproteinemia in chronic HCV infection with regard to abnormal apolipoproteins.

Ultrastructural organisation of HCV from the bloodstream of infected patients revealed by electron microscopy after specific immunocapture

“…Nevertheless, a widely accepted description of the putative structural organisation of LVPs has been published, depicting a hybrid particle consisting of lipoprotein and HCV components sharing a common envelope2 (figure 2E). However, this model has never been validated by TEM images of viral particles originating from a physiological sample, such as serum from an HCV+ patient.…”

Impact of interferon-free antivirus therapy on lipid profiles in patients with chronic hepatitis C genotype 1b

“…HCV particles in the peripheral blood are coated with lipids. About 10 8 HCV particles are assumed to be secreted from the liver into peripheral blood every 24 h[14]. This finding suggested that lipid metabolism is somewhat shifted towards the production of HCV particles.…”

Hepatitis C virus–apolipoprotein interactions: molecular mechanisms and clinical impact

“…Lipoproteins all have a common structure, consisting of a single outer layer of phospholipids, free cholesterol and amphipathic proteins that surrounds a non-polar core composed of triglycerides, cholesterol esters and fat-soluble components such as vitamins [5, 7]. The structure of a VLDL is illustrated in Figure 1.…”

“…Approximately 50% of IDL are cleared from the circulation through their interaction with hepatic remnant receptors and LDLR, while the remaining IDL can undergo further catabolism by the hepatic lipase (HL) to become LDL through the loss of ApoE. LDL have a high cholesterol content and provide cholesterol to peripheral tissues or liver cells via interaction of ApoB-100 with LDLR [7, 8]…”