Histone Deacetylase 3 Inhibitor Suppresses Hepatitis C Virus Replication by Regulating Apo-A1 and LEAP-1 Expression

作     者：Yuan Zhou Qian Wang Qi Yang Jielin Tang Chonghui Xu Dongwei Gai Xinwen Chen Jizheng Chen 

作者机构：State Key Laboratory of VirologyWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of SciencesBeijing 100101China Jiangsu Province Key Laboratory of Human Functional GenomiesDepartment of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjing 210029China 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2018年第33卷第5期

页      面：418-428页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 09[农学] 

基　　金：supported by the National Key Research and Development Program of China to YZ(2018YFA0507202) the Program for Youth Innovation Promotion Association in Chinese Academy of Science to JC 

主　　题：Hepatitis C virus (HCV) HDAC3 Apolipoprotein-A1 (Apo-A1) LEAP-1 Hepatocellular carcinoma Viral replication 

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 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 a (C/EBPa), hypoxia-inducible factor 1 a (HIF1 a), 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.