Virus Name | Hepatitis B virus |
Virus Short Name | HBV |
Order | Unassigned |
Virus Family | Hepadnaviridae |
Virus Subfamily | N.A. |
Genus | Orthohepadnavirus |
Species | Hepatitis B virus |
Host | Human, mammals |
Cell Tropism | Hepatocytes |
Associated Disease | Hepatitis, hepatocellular carcinoma(chronic infections), cirrhosis |
Mode of Transmission | Sexual contact, blood, maternal-neonatal |
VIPR DB link | N.A. |
ICTV DB link | https://talk.ictvonline.org/ictv-reports/ictv_9th_report/reverse-transcribing-dna-and-rna-viruses-2011/w/rt_viruses/155/hepadnaviridae |
Virus Host DB link | N.A. |
Paper Title | Sirtuin 1 Regulates Hepatitis B Virus Transcription and Replication by Targeting Transcription Factor AP-1 |
Author's Name | Ji-Hua Ren, Ying Tao, Zhen-Zhen Zhang, Wei-Xian Chen, Xue-Fei Cai, Ke Chen, Ben C. B. Ko, Chun-Li Song, Long-Kuan Ran, Wan-Yu Li, Ai-Long Huang, Juan Chen |
Journal Name | Journal Of Virology |
Pubmed ID | 24335313 |
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. |
Used Model | HepG2, Huh, HepG2.2.15 and HepG2-HBV1.1 cells |
DOI | 10.1128/JVI.02861-13 |