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Archives of Virology

, Volume 161, Issue 3, pp 621–630 | Cite as

The SIRT1 inhibitor, nicotinamide, inhibits hepatitis B virus replication in vitro and in vivo

  • Wan-Yu Li
  • Ji-Hua Ren
  • Na-Na Tao
  • Long-Kuan Ran
  • Xiang Chen
  • Hong-Zhong Zhou
  • Bo Liu
  • Xiao-Song Li
  • Ai-Long Huang
  • Juan ChenEmail author
Original Article

Abstract

We previously reported that SIRT1, an NAD+-dependent deacetylase belonging to the class III histone deacetylases, enhances hepatitis virus B (HBV) replication by targeting the transcription factor AP-1. However, the potential antiviral effects of nicotinamide, a SIRT1 inhibitor, have not yet been explored. In this study, we show that nicotinamide exhibits potent anti-HBV activity with little cytotoxicity. Nicotinamide suppressed both HBV DNA replicative intermediates and 3.5-kb mRNA expression. Moreover, nicotinamide treatment also suppressed core protein expression and the secretion of the hepatitis B surface antigen (HBsAg) and the hepatitis B e antigen (HBeAg) in HBV-expressing cell models. Importantly, nicotinamide treatment suppressed serum HBV DNA, HBsAg and HBeAg levels and liver HBV DNA in HBV-transgenic mice. Furthermore, using a dual-luciferase reporter assay, it was found that nicotinamide exhibited a marked inhibitory effect on the HBV core, SpI, SpII and X promoters, accompanied by decreased expression of the transcription factors AP-1, C/EBPα and PPARα. Therefore, nicotinamide suppresses HBV replication in vitro and in vivo by diminishing HBV promoter activity. This study highlights the potential application of nicotinamide in HBV therapy.

Keywords

Nicotinamide SIRT1 Inhibitor Nicotinamide Treatment SpII Promoter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by the National Natural Science Foundation of China 81201282 and 81472271.

Supplementary material

705_2015_2712_MOESM1_ESM.tif (25.8 mb)
Supplementary material 1 (TIFF 26425 kb)
705_2015_2712_MOESM2_ESM.doc (36 kb)
Supplementary material 2 (DOC 36 kb)

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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  • Wan-Yu Li
    • 1
  • Ji-Hua Ren
    • 1
  • Na-Na Tao
    • 1
  • Long-Kuan Ran
    • 1
  • Xiang Chen
    • 1
  • Hong-Zhong Zhou
    • 1
  • Bo Liu
    • 1
  • Xiao-Song Li
    • 1
  • Ai-Long Huang
    • 1
  • Juan Chen
    • 1
    Email author
  1. 1.The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of EducationChongqing Medical UniversityChongqingChina

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