Related Experiment Video
Updated: Jun 19, 2026

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
Published on: May 10, 2022
Enhanced intracellular retention of a hepatitis B virus strain associated with fulminant hepatitis
Jun Inoue1, Yoshiyuki Ueno, Futoshi Nagasaki
1Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai 980-8574, Japan. yueno@mail.tains.tohoku.ac.jp
Abstract:
A plasmid carrying 1.3-fold HBV genome was constructed from a HBV strain that caused five consecutive cases of fulminant hepatitis (pBFH2), and HepG2 cells were transfected with pBFH2 or its variants. The pBFH2 construct with A1762T/G1764A, G1862T, and G1896A showed the largest amount of core particle-associated intracellular HBV DNA, but no significant increase of extracellular HBV DNA in comparison with the wild construct, suggesting that these mutations might work together for retention of the replicative intermediates in the cells. The retention might relate to the localization of hepatitis B core antigen (HBcAg) in the nucleus of HepG2, which was observed by confocal fluorescence microscopy. HBcAg immunohistochemical examination of liver tissue samples obtained from the consecutive fulminant hepatitis patients showed stronger staining in the nucleus than acute hepatitis patients. In conclusion, the fulminant HBV strain caused retention of the core particles and the core particle-associated HBV DNA in the cells.
Insights
Fulminant hepatitis B virus (HBV) strains may retain viral DNA within cells. Specific mutations in the HBV genome appear to cause this retention, potentially linked to hepatitis B core antigen localization.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Fulminant hepatitis is a severe liver disease.
- Hepatitis B virus (HBV) is a major cause of liver disease worldwide.
- Specific HBV mutations are associated with disease severity.
Purpose of the Study:
- To investigate the role of specific HBV mutations in fulminant hepatitis.
- To determine the effect of these mutations on HBV replication and DNA retention.
Main Methods:
- Construction of a plasmid with a 1.3-fold HBV genome from a fulminant hepatitis strain (pBFH2).
- Transfection of HepG2 cells with pBFH2 and its variants.
- Quantification of intracellular and extracellular HBV DNA.
- Confocal fluorescence microscopy to observe hepatitis B core antigen (HBcAg) localization.
- Immunohistochemical examination of liver tissue samples.
Main Results:
- Mutations A1762T/G1764A, G1862T, and G1896A in pBFH2 led to the highest levels of core particle-associated intracellular HBV DNA.
- These mutations did not significantly increase extracellular HBV DNA.
- HBcAg was localized in the nucleus of HepG2 cells transfected with pBFH2.
- Stronger nuclear HBcAg staining was observed in liver tissues from fulminant hepatitis patients compared to acute hepatitis patients.
Conclusions:
- The studied HBV strain and its mutations promote the retention of replicative intermediates within cells.
- Nuclear localization of HBcAg may be associated with this retention mechanism.
- Fulminant HBV strains contribute to the intracellular accumulation of core particles and HBV DNA.
Related Concept Videos
Hepatitis
Viral Hepatitis I: Introduction
Viruses with RNA Genomes
Hepatic Drug Excretion: Enterohepatic Cycling
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Hepatic Drug Excretion: Influencing Factors
