Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein.
Intercellular adhesion molecule 1 (ICAM-1), a counter-receptor for lymphocyte function-associated antigen 1 on T cells, is critically important to a wide variety of adhesion-dependent leukocyte functions, including antigen presentation and target cell lysis. ICAM-1 expression by hepatocytes is increased in areas of inflammation and necrosis during chronic hepatitis B. Whether induction of ICAM-1 is due to the effect of inflammatory cytokines or involves a direct effect of the hepatitis B virus (HBV) remains unknown. In the present study, transfection of the HBV genome into human hepatoma cell lines resulted in enhanced expression of ICAM-1 protein and RNA in the absence of inflammation. Results of subgenomic transfections indicated that the HBV X protein (pX) induced ICAM-1 expression. Nuclear run-on assays showed that pX induced the ICAM-1 gene by increasing its rate of transcription. Although both pX and interferon gamma induced transcription of ICAM-1, addition of interferon gamma to cells expressing pX did not show an additive or synergistic effect. These results indicate that pX can directly regulate expression of ICAM-1 and may participate in the immunopathogenesis of HBV infection.
Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
K Q
KQ
Hu
C H
CH
Yu
J M
JM
Vierling
D015815:Cell Adhesion Molecules / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005796:Genes; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma / Q000494:pharmacology; D008099:Liver / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins
D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D015534:Trans-Activators; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma