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

The SIRT1 inhibitor, nicotinamide, inhibits hepatitis B virus replication in vitro and in vivo 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

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

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Publisher
Springer Vienna
Copyright
Copyright © 2016 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-015-2712-8
Publisher site
See Article on Publisher Site

References

  • Use of Niacin as a Drug
    DiPalma, JR; Thayer, WS
  • Nicotinamide reduces acute cortical neuronal death and edema in the traumatically injured brain
    Hoane, MR; Gilbert, DR; Holland, MA; Pierce, JL
  • Hepatitis B virus X protein: a multifunctional viral regulator
    Murakami, S
  • Nicotinamide inhibits HIV-1 in both acute and chronic in vitro infection
    Murray, MF; Srinivasan, A
  • Control of hepatitis B virus at the level of transcription
    Quasdorff, M; Protzer, U
  • SIRT2 regulates ciliogenesis and contributes to abnormal centrosome amplification caused by loss of polycystin-1
    Zhou, X; Fan, LX; Li, K; Ramchandran, R; Calvet, JP; Li, X

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