Disclosure Statement: No conflicts of interest exist.
Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication
Article first published online: 18 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 9, pages 1987–1996, September 2013
How to Cite
Sato, A., Saito, Y., Sugiyama, K., Sakasegawa, N., Muramatsu, T., Fukuda, S., Yoneya, M., Kimura, M., Ebinuma, H., Hibi, T., Ikeda, M., Kato, N. and Saito, H. (2013), Suppressive effect of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) on hepatitis C virus replication. J. Cell. Biochem., 114: 1987–1996. doi: 10.1002/jcb.24541
- Issue published online: 18 JUL 2013
- Article first published online: 18 JUL 2013
- Accepted manuscript online: 20 MAR 2013 07:28AM EST
- Manuscript Accepted: 5 MAR 2013
- Manuscript Received: 16 AUG 2012
- The Japan Society for the Promotion of Science (JSPS)
- Grant-in-Aid for Young Scientists A. Grant Number: 23680090
- Grant-in-Aid for Scientific Research C. Grant Number: 24590993
- Keio Gijuku Academic Development Fund
- Takeda Science Foundation
- Inaida Foundation
- SUBEROYLANILIDE HYDROXAMIC ACID;
- HEPATITIS C VIRUS;
The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) has a clinical promise for treatment of cancer including hepatocellular carcinoma (HCC). To investigate effect of SAHA on hepatitis C virus (HCV) replication, we treated the HCV replicon cell OR6 with SAHA. HCV replication was significantly inhibited by SAHA at concentrations below 1 μM with no cellular toxicity. Another HDAC inhibitor, tricostatin A, also showed reduction of HCV replication. The microarray analysis and quantitative RT-PCR demonstrated up-regulation of osteopontin (OPN) and down-regulation of apolipoprotein-A1 (Apo-A1) after SAHA treatment. Direct gene induction of OPN and knockdown of Apo-A1 also showed reduction of HCV replication. The liver specific microRNA-122, which is involved in HCV replication, was not affected by SAHA treatment. These results suggest that SAHA has suppressive effect on HCV replication through alterations of gene expression such as OPN and Apo-A1 in host cells. Epigenetic treatment with HDAC inhibitors may be a novel therapeutic approach for diseases associated with HCV infection such as chronic hepatitis, liver cirrhosis, and HCC. J. Cell. Biochem. 114: 1987–1996, 2013. © 2013 Wiley Periodicals, Inc.