title: Sirtuin 1 regulates hepatitis B virus transcription and replication by targeting transcription factor AP-1.
abstract: Chronic hepatitis B virus (HBV) infection is a major risk factor for liver cirrhosis and hepatocellular carcinoma. Nevertheless, the molecular mechanism of HBV replication remains elusive. SIRT1 is a class III histone deacetylase that is a structure component of the HBV cccDNA minichromosome. In this study, we found by using microarray-based gene expression profiling analysis that SIRT1 was upregulated in HBV-expressing cells. Gene silencing of SIRT1 significantly inhibited HBV DNA replicative intermediates, 3.5-kb mRNA, and core protein levels. In contrast, the overexpression of SIRT1 augmented HBV replication. Furthermore, SIRT1 enhanced the activity of HBV core promoter by targeting transcription factor AP-1. The c-Jun subunit of AP-1 was bound to the HBV core promoter region, as demonstrated by using a chromatin immunoprecipitation assay. Mutation of AP-1 binding site or knockdown of AP-1 abolished the effect of SIRT1 on HBV replication. Finally, SIRT1 inhibitor sirtinol also suppressed the HBV DNA replicative intermediate, as well as 3.5-kb mRNA. Our study identified a novel host factor, SIRT1, which may facilitate HBV replication in hepatocytes. These data suggest a rationale for the use of SIRT1 inhibitor in the treatment of HBV infection.
authors: The Second Affiliated Hospital and the Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, China.
authors: Ji-Hua
authors: JH
authors: Ren
authors: Ying
authors: Y
authors: Tao
authors: Zhen-Zhen
authors: ZZ
authors: Zhang
authors: Wei-Xian
authors: WX
authors: Chen
authors: Xue-Fei
authors: XF
authors: Cai
authors: Ke
authors: K
authors: Chen
authors: Ben C B
authors: BC
authors: Ko
authors: Chun-Li
authors: CL
authors: Song
authors: Long-Kuan
authors: LK
authors: Ran
authors: Wan-Yu
authors: WY
authors: Li
authors: Ai-Long
authors: AL
authors: Huang
authors: Juan
authors: J
authors: Chen
mesh_terms: D002460:Cell Line; D015870:Gene Expression; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D005814:Genes, Viral; D006515:Hepatitis B virus / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D056564:Sirtuin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014158:Transcription, Genetic; D014779:Virus Replication / Q000187:drug effects
chemical_list: D056572:Histone Deacetylase Inhibitors; D018808:Transcription Factor AP-1; D056564:Sirtuin 1