HBx protein induces expression of MIG and increases migration of leukocytes through activation of NF-kappaB

Virology. 2009 Mar 15;385(2):335-42. doi: 10.1016/j.virol.2008.11.042. Epub 2009 Jan 20.

Abstract

Elevated expression of monokine induced by the interferon-gamma (MIG) has been shown in HBV carriers, and it is involved in the infiltration of inflammatory cells and liver damage after HBV infection. However, the molecular mechanisms by which HBV-induced MIG expression have not been characterized. Our results indicated that HBx protein induced MIG expression in a dose-dependent manner. Such increase was due to the direct binding of NF-kappaB to the MIG promoter. By luciferase, chromatin immunoprecipitation and electrophoretic mobility shift assays, we demonstrated that the NF-kappaB binding site at positions -147 was essential for transcriptional activation of MIG promoter by HBx protein. Chemotaxis assay showed that the up-regulation of MIG protein levels enhanced the migration of peripheral blood lymphocytes (PBLs), and inhibition of NF-kappaB significantly decreased the chemotaxis activity. Our findings provide a new insight into how leukocytes migrate to liver, and disclose a new regulatory mechanism of MIG expression after HBV infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Nucleus / metabolism
  • Chemokine CXCL9 / genetics
  • Chemokine CXCL9 / metabolism*
  • Gene Expression Regulation*
  • Hepatocytes / metabolism
  • Hepatocytes / virology
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / physiology
  • Molecular Sequence Data
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Transport
  • Trans-Activators / metabolism*
  • Viral Regulatory and Accessory Proteins / metabolism*

Substances

  • CXCL9 protein, human
  • Chemokine CXCL9
  • NF-kappa B
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein