Hepatitis C Virus Particles and Lipoprotein Metabolism

Abstract

The majority of infectious hepatitis C particles are present in the low-density fractions from plasma of infected patients, suggesting an association of the virus with lipoproteins and the use of lipoprotein receptors for cell entry. Although classical hepatitis C virus (HCV) virions have been reported by some investigators, their role in the HCV life cycle has not been clearly identified. Moreover, two other forms of particles have been characterized: low-density lipo-viro-particles (LVPs) and high-density particles. The latter are nonenveloped nucleocapsids that have immunoglobulin G Fcgamma binding capacity. LVPs are spherical particles enriched in triglycerides. At a minimum, they contain apolipoprotein B, HCV RNA, and core protein. The main source of LVPs is likely to be the enterocytes rather than the hepatocytes, suggesting an interaction between chylomicron and LVP assembly. In experimental systems, HCV core protein inhibits the microsomal triglyceride transfer protein, binds to apolipoprotein AII, and induces accumulation of cytoplasmic lipid droplets. A model of LVP and HCV core-lipid droplet generation is proposed.

Role of Phosphatidylinositol 4-Phosphate (PI4P) and Its Binding Protein GOLPH3 in Hepatitis C Virus Secretion

“…The occurrence of VLDL-associated viral particles (lipoviroparticles) in patient sera further strengthen the notion that HCV and VLDL secretion overlap and that HCV co-opts the VLDL secretory pathway for its secretion (50). Although the intricate details of VLDL biogenesis are still unclear, it is well known that the VLDL particles traffic through the Golgi compartments, implicating a similar pathway for HCV virion egress (19,51).…”

HCV‐specific T‐cell responses in injecting drug users: evidence for previous exposure to HCV and a role for CD4+ T cells focussing on nonstructural proteins in viral clearance

“…We did observe lower HCV-RNA plasma concentrations in resolvers compared to chronic carriers, but it remains speculative whether higher HCV-RNA concentrations lead to more circulating Core protein. It has been suggested that serum of HCV-infected individuals contains virus particles with HCV Core epitopes exposed on their surfaces [37] and that serum may contain free circulating Core proteins [38]. In addition, HCV Core is thought to play a role in modulating immune responses by affecting the function of virus-specific T cells [36,39,40].…”

Hepatitis c virus and host cell lipids: An intimate connection

“…2). In this respect, HCV circulating in the blood of infected patients biochemically resembles a VLDL particle, 76 by being rich in cholesteryl esters and containing apolipoproteins such as ApoE and ApoB (Fig. 2).…”