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. Archives of Virology Springer Journals

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

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Springer Vienna
Copyright © 2016 by Springer-Verlag Wien
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
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