Tg1.4HBV-s-rec mice, a crossbred hepatitis B virus-transgenic model, develop mild hepatitis.

Abstract

Hepatitis B virus (HBV)-transgenic mice exhibit competent innate immunity and are therefore an ideal model for considering intrinsic or cell-based mechanisms in HBV pathophysiology. A highly replicative model that has been little used, let alone characterized, is the Tg1.4HBV-s-rec strain derived from cross breeding of HBV-transgenic mouse models that either accumulate (Alb/HBs, Tg[Alb1-HBV]Bri44) or lack (Tg1.4HBV-s-mut) the hepatitis B surface antigen (HBsAg). Tg1.4HBV-s-rec hepatocytes secreted HBsAg, Hepatitis B extracellular antigen (HBeAg) and produced HBV virions. Transmission electron microscopy visualised viral particles (Tg1.4HBV-s-rec), nuclear capsid formations (Tg1.4HBV-s-mut and Tg1.4HBV-s-rec) and endoplasmic reticulum malformations (Alb/HBs). Viral replication in Tg1.4HBV-s-rec and Tg1.4HBV-s-mut differed in HBsAg expression and interestingly in the distribution of HBV core antigen (HBcAg) and HBV × protein. While in Tg1.4HBV-s-mut hepatocytes, the HBcAg was located in the cytoplasm, in Tg1.4HBV-s-rec hepatocytes, the HBcAg appeared in the nuclei, suggesting a more productive replication. Finally, Tg1.4HBV-s-rec mice showed symptoms of mild hepatitis, with reduced liver function and elevated serum transaminases, which appeared to be related to natural killer T cell activation. In conclusion, the study of Alb/HBs, Tg1.4HBV-s-mut and their F1 progeny provides a powerful tool to elucidate HBV pathophysiology, especially in the early HBeAg-positive phases of chronic infection and chronic hepatitis.

• Authors: Stefan Schefczyk, Xufeng Luo, Yaojie Liang, Mike Hasenberg, Bernd Walkenfort, Martin Trippler, Jonas Schuhenn, Kathrin Sutter, Mengji Lu, Heiner Wedemeyer, Hartmut H Schmidt, Ruth Broering
• Journal: Scientific reports (Sci Rep) Vol. 13 Issue 1 Pg. 22829 (12 20 2023) ISSN: 2045-2322 [Electronic] England
• PMID: 38129531 (Publication Type: Journal Article)
• Copyright: © 2023. The Author(s).

Chemical References

• Hepatitis B Surface Antigens
• Hepatitis B Core Antigens
• Hepatitis B e Antigens
• Hepatitis B Antigens
• DNA, Viral

Topics

• Mice
• Animals
• Hepatitis B virus (physiology)
• Hepatitis B Surface Antigens (genetics)
• Hepatitis B Core Antigens
• Hepatitis B e Antigens (genetics)
• Hepatitis B Antigens
• Hepatitis A
• Virus Replication
• Mice, Transgenic
• Hepatitis B
• DNA, Viral
• Liver