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There is a relationship between the life cycle of the hepatitis C virus (HCV) and the synthesis and hemostasis of lipids as well as lipid metabolism and interferon (IFN) regulatory system. This study aimed to examine the effect of fluvastatin and IFN-γ in the expression of mediators involved in lipid metabolism and HCV proliferation in patients with rs12979860 CC polymorphism. Thirteen patients with HCV and five controls with rs1297986CC polymorphism were included in this study. Peripheral blood mononuclear cells (PBMCs) of patients and controls were treated by fluvastatin, IFN-γ or fluvastatin+IFN-γ. Assessment of IL-28B polymorphism, RNA extraction, and quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed. The mRNA expression of sterol regulatory element-binding protein 1 c (SREBP1c), ATP-binding cassette transporter A1 (ABCA1), diacylglycerol acyltransferase 1 (DGAT1), and HCV core as well as measurement of ABCA1 protein level were evaluated before and after treatment. The results indicated that IFN-γ +fluvastatinacted as an inhibitor in mRNA expression of SREBP1c; while acting as an inducer in the expression of ABCA-1. The results of ABCA1 assay showed a significant increase of this protein after treatment with fluvastatin and IFN-γ compared with untreated cells (p=0.02). Moreover, the mRNA expression of HCV core was suppressed in all experimental groups treated with fluvastatin, IFN-γ or their combination which was more significant after treatment with fluvastatin+IFN-γ (p<0.001). The results of this study demonstrated the significant effect of treatment with fluvastatin+IFN-γ in PBMCs of HCV patients with rs12979860 CC polymorphism. According to the drug resistance of viruses and prevention of virus-induced steatosis in patients with HCV, using regulatory agents of lipid mediators in parallel with current medications could be considered as an effective therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objective: Hepatitis C virus is a main cause of progressive and chronic liver disease such as hepatitis, cirrhosis and hepatocellular carcinoma which resulted in global health concern. There are 170 million people infecting HCV in the world. Autophagy is a catabolic process 'degrading damaged organelles and cellular components for recycling. There are conflict reports about the role of autophagy in production of cytokines in viral infection. It may depend on the type of virus and the type of infected cells. However, it has been reported that in HCV infected cells, dysfunction of autophagy led to enhancement in some products of native immunity factors such as interferon-α. HCV has been shown to induce autophagy to increase viral growth in vitro. Pharmacological inhibition of autophagic process remarkably inhibited expression level of HCV replicon. In this study we examined the impact of autophagy inhibition by chloroquine'a lysosomal acidification inhibitor'on IFNα mRNA expression and HCV replication in PBMCs. Material and Methods: Immediately after blood collection from HCV positive patients who have chronic HCV genotype1a before treatment the PBMCs were separated from whole blood by centrifugation on a Ficoll-Hypaque density gradient. The same number of normal samples were tested as controls. The cells were cultured in RPMI medium and incubated with 50μgr chloroquine. MTT assay was applied to indicate the dose of chloroquine that has minimum cytotoxicity for cells. After 72h, viral RNA was extracted. The real-time PCR was carried out after a reverse transcription step. The result had been analyzed by REST software. Results: The use of CQ for inhibition of autophagy in infected PBMCs with HCV resulted in a decrease amount HCV mRNA with an increase in IFNα mRNA expression. These results indicated that chloroquine may consider as a complementary new anti-HCV agent that targets the autophagic proteolysis. Conclusion: Inhibition of autophagy may be a new therapeutic strategy for HCV treatment. CQ (chloroquine), inhibits autophagy in infected PBMCs and led to increase of IFNα mRNA expression. This increase has an inhibitory effect on HCV replication. These findings imply that chloroquine effectively impairs the function of autophagy in our experiment. [ABSTRACT FROM AUTHOR]