title: The SIRT1 inhibitor, nicotinamide, inhibits hepatitis B virus replication in vitro and in vivo.
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.
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Ji-Hua
authors.initials: JH
authors.lastname: Ren
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Tao
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Long-Kuan
authors.initials: LK
authors.lastname: Ran
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Hong-Zhong
authors.initials: HZ
authors.lastname: Zhou
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: Li
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
authors.forename: Ai-Long
authors.initials: AL
authors.lastname: Huang
authors.affiliation: The Second Affiliated Hospital and The Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China. yixin_xinyuan@163.com.
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects* / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D008822:Mice, Transgenic; D009536:Niacinamide / Q000008:administration & dosage* / Q000494:pharmacology* / Q000633:toxicity; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D009536:Niacinamide; C447939:SIRT1 protein, human; D056564:Sirtuin 1