Stimulation of B7-H1 in hepatocarcinoma cells by hepatitis B virus X antigen

Immunol Invest. 2010;39(7):754-69. doi: 10.3109/08820139.2010.494193.


The cross-talk between the hepatitis B virus X protein (HBx) and B7-H1 in hepatocarcinoma (HCC) is unclear. This study analyzed the potential relationships between HBx and B7-H1 in hepatocarcinogenesis. One of human HCC cell lines, HepG2 cells, was transfected to stably express HBx protein (HBx(+)-HepG2). The transcription of B7-H1 mRNA was increased significantly in these cells compared to cells transfected with control vector (HBx(-)-HepG2), as confirmed by a comparative genome-wide microarray analysis (Capitalbio) and real time quantitative PCR (qPCR). Flow cytometry and western-blot further demonstrated that B7-H1 protein synthesis was enhanced in HBx(+)-HepG2 cells. Site-directed mutagenesis of promoter constructs revealed that the transcription factor (NF)-κB binding site between 128 and 137 bp upstream of B7-H1 gene transcriptional start site is primarily responsible for HBx-mediated B7-H1 expression. Co-culture experiments with HBx(+)-HepG2/T cells showed that the number of apoptotic T cells increased profoundly, and this effect could be partially prevented when a neutralizing mAb against B7-H1 was added to the culture, demonstrating that B7-H1 signaling can promote T cell apoptosis. Our results suggest that the expression of B7-H1 in hepatocarcimona cells can be initiated by HBx antigen, thus inducing T cell apoptosis and finally potentially facilitates the genesis of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Blocking / pharmacology
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism*
  • Apoptosis / drug effects
  • Apoptosis / immunology
  • B7-H1 Antigen
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / virology*
  • Coculture Techniques
  • Hep G2 Cells
  • Hepatitis B virus / immunology*
  • Humans
  • Microarray Analysis
  • NF-kappa B / metabolism
  • Promoter Regions, Genetic / immunology
  • Protein Binding / genetics
  • Protein Binding / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology
  • Transcriptional Activation / genetics
  • Transcriptional Activation / immunology
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology
  • Viral Fusion Proteins / metabolism*


  • Antibodies, Blocking
  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • NF-kappa B
  • Viral Fusion Proteins
  • X antigen, viral infections