Hepatitis C Virus Increases Free Fatty Acids Absorption and Promotes its Replication Via Down-Regulating GADD45? Expression.

ABSTRACT: BACKGROUND Hepatitis C virus (HCV) infection, as a major cause of chronic hepatic diseases, is always accompanied with an abnormality of lipid metabolism. The aim of this study was to investigate the pathogenic role of free fatty acids (FFA) in human HCV infection. MATERIAL AND METHODS Peripheral blood lipid indexes among HCV patients with different viral loads (199 samples) and healthy donors (80 samples) were detected by clinical biochemistry tests. HCV replication and the expression of growth arrest and DNA-damage-inducible gene 45-? (GADD45?) in Huh7 cells and clinical samples were quanti?ed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Lipid accumulation in Huh7 cells was detected by immunofluorescence. RESULTS In this study, we found that FFA showed a significant positive correlation with viral load in peripheral blood of HCV patients, but not total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). GADD45? expression in HCV patients dramatically decreased with the increase of viral load. In Huh7 cells, FFA treatment significantly enhanced HCV replication. HCV infection inhibited GADD45? expression, and this effect was further enhanced with the presence of FFA treatment. Ectopic expression of GADD45? in HCV-infected Huh7 cells markedly inhibited the absorption of FFA and HCV replication. However, FFA significantly elevated GADD45? expression without HCV infection. CONCLUSIONS These results demonstrated that HCV down-regulates GADD45? expression to enhance FFA absorption and thus facilitate its replication. GADD45? is an essential mediator for the pathogenesis of HCV infection. Thus, our study provides potential clues in the search for novel therapeutics and fatty lipid control options for HCV patients.

SUBMITTER: Chen W 

PROVIDER: S-EPMC4946386 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature