Sirtuin 1 regulates hepatitis B virus transcription and replication by targeting transcription factor AP-1

Ji Hua Ren, Ying Tao, Zhen Zhen Zhang, Wei Xian Chen, Xue Fei Cai, Ke Chen, Chi Bun Ko, Chun Li Song, Long Kuan Ran, Wan Yu Li, Ai Long Huang, Juan Chena

Research output: Journal article publicationJournal articleAcademic researchpeer-review

93 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)2442-2451
Number of pages10
JournalJournal of Virology
Issue number5
Publication statusPublished - 1 Mar 2014

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


Dive into the research topics of 'Sirtuin 1 regulates hepatitis B virus transcription and replication by targeting transcription factor AP-1'. Together they form a unique fingerprint.

Cite this