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Updated: Aug 8, 2026

Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
Published on: February 1, 2017
Up-regulation of intercellular adhesion molecule 1 transcription by hepatitis B virus X protein
1Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Insights
Hepatitis B virus (HBV) directly increases intercellular adhesion molecule 1 (ICAM-1) expression in liver cells. The HBV X protein (pX) drives this increase by enhancing ICAM-1 gene transcription, potentially impacting HBV immune responses.
Area of Science:
- Hepatology
- Immunology
- Virology
Background:
- Intercellular adhesion molecule 1 (ICAM-1) is crucial for leukocyte functions and its expression increases in chronic hepatitis B.
- The precise mechanism driving ICAM-1 induction during hepatitis B virus (HBV) infection is not fully understood.
Purpose of the Study:
- To investigate whether HBV directly induces ICAM-1 expression in hepatocytes.
- To identify the specific HBV component responsible for ICAM-1 induction.
Main Methods:
- Transfection of HBV genome into human hepatoma cell lines.
- Subgenomic transfection to pinpoint the responsible HBV protein.
- Nuclear run-on assays to assess gene transcription rates.
Main Results:
- HBV genome transfection enhanced ICAM-1 protein and RNA expression without inflammation.
- The HBV X protein (pX) was identified as the inducer of ICAM-1 expression.
- pX increased ICAM-1 gene transcription, and this effect was not additive with interferon gamma.
Conclusions:
- HBV can directly induce ICAM-1 expression in liver cells.
- The HBV X protein plays a direct role in regulating ICAM-1 expression.
- These findings suggest pX contributes to the immunopathogenesis of HBV infection.
Abstract:
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.
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