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

Virology
|October 24, 2009
PubMed

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.

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