Virologica Sinica

, Volume 33, Issue 5, pp 418–428 | Cite as

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

  • Yuan Zhou
  • Qian Wang
  • Qi Yang
  • Jielin Tang
  • Chonghui Xu
  • Dongwei Gai
  • Xinwen Chen
  • Jizheng Chen
Research Article


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.


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



We would like to thank the members of Chen’s lab and the core facilities center of Wuhan institute of virology for technical help. This study was supported by the National Key Research and Development Program of China to YZ (2018YFA0507202) and the Program for Youth Innovation Promotion Association in Chinese Academy of Science to JC.

Author Contributions

JC conceived/designed the experiments. YZ and QW performed the experiments and analyzed the data. YQ, JT, XC and DG contributed reagents/materials/analysis tools. JC and XC wrote the manuscript. YZ and QW prepared the figures and tables. JC checked and finalized the manuscript. All authors read and approved the final manuscript.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Animal and Human Rights Statement

The study was approved by the Animal Ethics Committee of Wuhan Institute of Virology. All institutional and national guidelines for the care and use of laboratory animals were followed.

Supplementary material

12250_2018_57_MOESM1_ESM.pdf (627 kb)
Supplementary material 1 (PDF 628 kb)
12250_2018_57_MOESM2_ESM.xlsx (115 kb)
Supplementary material 2 (XLSX 115 kb)


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Copyright information

© Wuhan Institute of Virology, CAS and Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.State Key Laboratory of VirologyWuhan Institute of Virology, Chinese Academy of SciencesWuhanChina
  2. 2.University of Chinese Academy of SciencesBeijingChina
  3. 3.Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular BiologyNanjing Medical UniversityNanjingChina

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