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Published on: September 25, 2019
Transgenic mice replicating hepatitis B virus but lacking expression of the major HBsAg
Leonie Halverscheid1, Nina K Mannes, Robert Weth
1Department of Medicine II, University Hospital Freiburg, Freiburg, Germany.
Abstract:
Hepatitis B Virus (HBV) transgenic mice replicating the viral genome at high level but lacking expression of the small envelope protein (HBsAg) have been produced using a terminally redundant viral DNA construct (HBV 1.4). The generation of viable infectious progeny was dependent on sex and age of mice. Viral mRNA was abundant in liver and kidneys and at low levels in other organs of the mice. No viral particles or HBV envelope proteins could be detected in sera of mice. Despite expression of non-secreted LHBs and MHBs proteins in the liver, there was no accumulation of viral particles in the endoplasmic reticulum of hepatocytes and no necroinflammatory hepatitis was observed. Therefore, these mice represent an excellent model for studies of the role of HBsAg in viral assembly, antiviral immune responses, the further understanding of HBV immunopathogenesis, and the development of antiviral vaccines.
Insights
New Hepatitis B Virus (HBV) transgenic mice lack small envelope protein (HBsAg) expression. These mice are valuable for studying HBV assembly, immune responses, and developing new antiviral vaccines.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Hepatitis B Virus (HBV) infection is a major global health concern.
- The small envelope protein (HBsAg) plays a critical role in HBV assembly and pathogenesis.
- Understanding HBsAg's function is crucial for developing effective antiviral strategies and vaccines.
Purpose of the Study:
- To generate and characterize HBV transgenic mice lacking HBsAg expression.
- To investigate the role of HBsAg in viral replication, assembly, and pathogenesis.
- To establish a novel animal model for HBV research.
Main Methods:
- Generation of transgenic mice using a terminally redundant viral DNA construct (HBV 1.4).
- Analysis of viral mRNA expression in various organs.
- Detection of viral particles and proteins in sera and liver tissue.
- Histopathological examination of liver for signs of inflammation.
Main Results:
- Transgenic mice successfully replicated the HBV genome but lacked HBsAg expression.
- Viral mRNA was detected in liver and kidneys.
- No infectious progeny, viral particles, or HBsAg were found in sera.
- Hepatocytes showed expression of non-secreted LHBs and MHBs proteins without endoplasmic reticulum accumulation or necroinflammatory hepatitis.
Conclusions:
- The generated HBV transgenic mice lacking HBsAg are a viable model for studying HBV immunopathogenesis.
- This model is suitable for investigating the role of HBsAg in viral assembly and antiviral immune responses.
- These mice offer a promising platform for the development of novel antiviral vaccines against HBV.
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