Hepatitis C Virus Uses Host Lipids to Its Own Advantage

Abstract

Lipids and lipoproteins constitute indispensable components for living not only for humans. In the case of hepatitis C virus (HCV), the option of using the products of our lipid metabolism is “to be, or not to be”. On the other hand, HCV infection, which is the main cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, exerts a profound influence on lipid and lipoprotein metabolism of the host. The consequences of this alternation are frequently observed as hypolipidemia and hepatic steatosis in chronic hepatitis C (CHC) patients. The clinical relevance of these changes reflects the fact that lipids and lipoprotein play a crucial role in all steps of the life cycle of HCV. The virus circulates in the bloodstream as a highly lipidated lipo-viral particle (LVP) that defines HCV hepatotropism. Thus, strict relationships between lipids/lipoproteins and HCV are indispensable for the mechanism of viral entry into hepatocytes, viral replication, viral particles assembly and secretion. The purpose of this review is to summarize the tricks thanks to which HCV utilizes host lipid metabolism to its own advantage.

The Impact of Steatosis on Chronic Hepatitis C Progression and Response to Antiviral Treatments

“…Results showed that the overall changes in CAP were significantly elevated at SVR24; moreover, these changes were negatively correlated with baseline values of steatosis, whereby, in patients with severe steatosis at baseline, CAP values were decreased while those with lower baseline of steatosis experienced elevation of CAP. Since the impairment of VLDL secretion as a result of downregulation of MTP has been known to cause hypocholesterolemia and decreased triglyceride levels in HCV patients [114], successful treatment with DAAs might lead to elevation of LDL-C and triglycerides [115,116]. A summary of the response to IFN-based and IFN-free DAAs in HCV-associated steatosis is illustrated in Figure 4.…”

PPAR Ligands Induce Antiviral Effects Targeting Perturbed Lipid Metabolism during SARS-CoV-2, HCV, and HCMV Infection

“…Consequently, hypolipidemia and hepatic steatosis are conditions frequently occurring in chronic hepatitis C patients. These metabolic changes in host highlight the close interplay between HCV and the lipid metabolism, with lipids and lipoproteins playing a crucial role in the virus lifecycle [ 45 ]. A strict relationship between lipids and HCV is necessary for the mechanism of viral entry into hepatocytes, replication, particles assembly and secretion [ 46 ].…”

Domain 2 of Hepatitis C Virus Protein NS5A Activates Glucokinase and Induces Lipogenesis in Hepatocytes

“…HCV core protein was reported to interact with host lipid droplets, thus dysregulating lipid turnover and promoting LVP assembly [12,13]. Additionally, HCV infection induces the activation of Sterol Regulatory Element-Binding Protein (SREBP), the transcription factor responsible for lipogenesis [14,15]. Downregulation of carnitine palmitoyltransferase expression may additionally increase steatosis by inhibition of beta-oxidation [16].…”

“…These observations highlight the necessity for HCV to interfere with lipid metabolism but the lack of a metabolically competent cell line mimicking hepatic lipogenesis and lipoprotein synthesis has significantly hampered our understanding of this phenomenon [8,15,19,21]. Indeed, the in vitro assembly of bona fide infectious LVPs was only observed in primary human hepatocytes that are functional for the production of very low-density lipoproteins (VLDLs).…”