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

Author:
Li, Wan-Yu, Ren, Ji-Hua, Tao, Na-Na, Ran, Long-Kuan, Chen, Xiang, Zhou, Hong-Zhong, Liu, Bo, Li, Xiao-Song, Huang, Ai-Long, Chen, Juan
Source:
Archives of virology 2016 v.161 no.3 pp. 621-630
ISSN:
0304-8608
Subject:
DNA, Hepatitis B virus, antiviral properties, blood serum, cytotoxicity, gene expression, hepatitis B antigens, histone deacetylase, liver, messenger RNA, mice, models, nicotinamide, protein synthesis, secretion, therapeutics, transcription factors, virus replication
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.
Agid:
5061825