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

Autor: Schefczyk S; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany., Luo X; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.; Institute for Lymphoma Research, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China., Liang Y; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany., Hasenberg M; Electron Microscopy Unit, Imaging Center Essen, Medical Faculty, Germany Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Walkenfort B; Electron Microscopy Unit, Imaging Center Essen, Medical Faculty, Germany Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Trippler M; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany., Schuhenn J; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Sutter K; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Lu M; Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Wedemeyer H; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany.; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Schmidt HH; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany., Broering R; Department of Gastroenterology, Hepatology and Transplant Medicine, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany. ruth.broering@uni-due.de.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Dec 20; Vol. 13 (1), pp. 22829. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1038/s41598-023-50090-8
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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