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  • Author: Jin-ling Dong x
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Molecular Pathogenesis of Liver Steatosis Induced by Hepatitis C Virus

Abstract

Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC). Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV) infection. Level of low density lipoprotein receptor (LDL-R) and activity of peroxisome proliferator-activated receptor (PPAR) α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP), and formation of very low density lipoprotein (VLDL) have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP)-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN), HMG CoA reductase (HMGCR), liver X receptor (LXR), acetyl-CoA carboxylase 1 (ACC1), hepatic CB (1) receptors, retinoid X receptor (RXR) α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.

Open access
Inhibition on IFN-β Expression by HCV NS3 and NS5A in HepG2 Cells

Abstract

Objective To observe the effects of HCV protein, NS3 and NS5A on IFN-β in HepG2 cells and its regulation mechanism.

Methods Human liver hepatocellular carcinoma cells HepG2 were transfected with recombinant eukaryotic plasmid pcDNA3.1/myc-His-core, NS3 or NS5A to overexpress these proteins, and the expression of IFN-β were detected by qRT-PCR, Western blotting and ELISA. Luc2P reporter plasmids pGL4.10-IFNβ-P were constructed and transfected into HepG2 cells, and the activity of IFN-β promoter were determined through luciferase assay for regulation mechanism study.

Results Both mRNA level and protein expression of IFN-β were significantly decreased (P < 0.05) in the presence of NS3 or NS5A protein. Luciferase assay revealed that NS3 or NS5A protein downregulated IFN-β promoter activity (P < 0.05). Meanwhile, HCV core protein had little effect on IFN-β expression.

Conclusions HCV protein NS3 and NS5A could inhibit innate IFN-β expression and thus escape immune selection and hinder the host immune responses.

Open access