1 State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China
2 University of Chinese Academy of Sciences, Beijing 100101, China
3 Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing 210029, China
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 1α (HIF1α), 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.