【摘 要】
：
Histone deacetylase (HDAC) inhibitors show clinical promise for the treatment of cancers,including hepatocellular carcinoma (HCC).In this study,we investigated the effect of HDAC inhibitor treatment on hepatitis C virus (HCV)replication in Huh7 human live
【机 构】
：
State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 43
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Histone deacetylase (HDAC) inhibitors show clinical promise for the treatment of cancers,including hepatocellular carcinoma (HCC).In this study,we investigated the effect of HDAC inhibitor treatment on hepatitis C virus (HCV)replication in Huh7 human liver cells and in a mouse model of HCV infection.Viral replication was markedly suppressed by the HDAC3 inhibitor at concentrations below 1 mmol/L,with no cellular toxicity.This was accompanied by upregulation of liver-expressed antimicrobial peptide 1(LEAP-1) and downregulation of apolipoprotein-A1 (Apo-A1),as determined by microarray and quantitative RT-PCR analyses.Moreover,HDAC3 was found to modulate the binding of CCAAT-enhancer-binding protein α (C/EBPα),hypoxia-inducible factor 1 α (HIF1 α),and signal transducer and activator of transcription 3 (STAT3) to the LEAP-1 promoter.HDAC3 inhibitor treatment also blocked HCV replication in a mouse model of HCV infection.These results indicate that epigenetic therapy with HDAC3 inhibitor may be a potential treatment for diseases associated with HCV infection such as HCC.
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