Repression of hepatitis B viral gene expression by transcription factor nuclear factor-kappaB.
Infection of human hepatitis B virus (HBV) causes acute hepatitis. Its persistent infection leads to a high risk of developing chronic hepatitis, cirrhosis and hepatocellular carcinoma. The levels of HBV 3.5 kb and 2.4/2.1 kb RNAs transcribed from a replicating HBV expression plasmid in human hepatoma HuH-7 cells are repressed by tumour necrosis factor alpha treatment or overexpressed p65 in a dose-dependent manner. The diminished expression of endogenous p65 by a p65-specific siRNA or IkappaB-alpha overexpression enhances the HBV gene expression. The protein bound to the Specificity protein 1 (Sp1) binding sites (nt 1733-1753) of HBV core promoter is reduced by either tumour necrosis factor alpha treatment or overexpressed p65. The N-terminal 43-amino-acid region of p65, which is required to interact with Sp1, is essential to repress the Sp1-mediated transactivation. The binding of Sp1 to Sp1 site and the Sp1-dependent reporter expression are inhibited by p65 in a dose-dependent manner. Furthermore, nuclear factor-kappa B-mediated repression of HBV gene expression is abolished by deletion of Sp1 sites of HBV gene promoter. Together, these results demonstrate that nuclear factor-kappa B represses the HBV gene expression through its interaction with Sp1 and repression of Sp1-mediated transcriptional activation.
Lin
Yen-Cheng
YC
Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Pei-Tou, Taipei 11221, Taiwan, Republic of China.
Hsu
En-Chi
EC
Ting
Ling-Pai
LP
D002460:Cell Line; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D017781:Genes, Immediate-Early; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015533:Transcriptional Activation; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*
D017874:Immediate-Early Proteins; D016328:NF-kappa B; D016329:Sp1 Transcription Factor; D014764:Viral Proteins