Hepatitis C virus particles and lipoprotein metabolism

Area of Science:

• Hepatology
• Virology
• Lipid Metabolism

Background:

• Infectious hepatitis C particles are predominantly found in low-density plasma fractions.
• This suggests an association of hepatitis C virus (HCV) with lipoproteins and potential use of lipoprotein receptors for cell entry.
• While classical HCV virions exist, their role in the viral life cycle remains unclear, with other particle forms like LVPs and high-density particles also characterized.

Purpose of the Study:

• To investigate the nature and origin of infectious hepatitis C particles.
• To elucidate the role of lipoproteins in HCV infection and cell entry.
• To propose a model for LVP and HCV core-lipid droplet generation.

Main Methods:

• Analysis of low-density plasma fractions from infected patients.
• Characterization of low-density lipo-viro-particles (LVPs) and high-density particles.
• Experimental systems to study HCV core protein interactions with lipid metabolism factors.

Main Results:

• The majority of infectious HCV particles are associated with lipoproteins in low-density fractions.
• LVPs are spherical, triglyceride-enriched particles containing apolipoprotein B, HCV RNA, and core protein.
• LVPs likely originate from enterocytes, suggesting chylomicron and LVP assembly interactions.
• HCV core protein was shown to inhibit microsomal triglyceride transfer protein and bind apolipoprotein AII, leading to lipid droplet accumulation.

Conclusions:

• Infectious HCV predominantly circulates as LVPs, linked to lipoproteins and potentially utilizing lipoprotein receptors for cell entry.
• LVPs appear to originate from enterocytes, indicating a connection with chylomicron assembly.
• HCV core protein influences lipid metabolism, contributing to LVP formation and lipid droplet accumulation.