Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

Daniel Felmlee,Thomas Baumert,Mohamed Hafirassou,Catherine Schuster,Mathieu Lefevre

doi:10.3390/v5051292

Abstract

Hepatitis C virus (HCV) is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL) assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects.

Highlights

For the approximately 170 million individuals infected with hepatitis C virus (HCV), there is no vaccine available and the standard of care therapeutic options prior to inclusion of direct antiviral agents (DAAs) have been effective for only 50% of patients, for the most prevalent phylogenetically distinct group by 30% nucleotide sequence, genotype 1 [1]
The authors of this study propose that apoC-III levels may potentially act as a possible marker of Hepatitis C virus (HCV) disease progression [62]
These data indicate the close association between HCV glycoproteins and host cell lipoproteins even in the absence of viral capsids, a finding recently confirmed in observations of E1/apoB interactions [123]

Summary

Introduction

For the approximately 170 million individuals infected with hepatitis C virus (HCV), there is no vaccine available and the standard of care therapeutic options prior to inclusion of direct antiviral agents (DAAs) have been effective for only 50% of patients, for the most prevalent phylogenetically distinct group by 30% nucleotide sequence, genotype 1 [1]. The functional advantage of the association of virions with host lipoproteins has not been completely elucidated, though evidence suggests utilization of lipoprotein components may both mediate attachment to lipoprotein receptors, and obscure circulating viral particles from immunoglobulin recognition, thereby allowing the virus to escape immune surveillance [14,15] It must be determined whether these mechanisms are clear priorities, given the implications in vaccine design and the possibility that abrogating these mechanisms may have important clinical significance in preventing infection post-liver transplantation [16,17]. Several studies have indicated a link between the successful outcome of antiviral treatment and observed lipid metabolism parameters of the patient Both hepatic steatosis and insulin resistance impair treatment response to interferon α (IFNα) [63,64,65]. The association of lipids with peg-interferon treatment response suggests that lipid modulation may be an effective strategy to modify interferon sensitivity [71,73]

Treatments Targeting Lipid Metabolism

Apolipoproteins and the Viral Particle

Lipoprotein and Cholesterol’s Role in Viral Entry

Findings

Cholesterol and Viral Replication