Enhanced intracellular retention of a hepatitis B virus strain associated with fulminant hepatitis

Jun Inoue, Yoshiyuki Ueno, Futoshi Nagasaki, Yuta Wakui, Yasuteru Kondo, Koji Fukushima, Hirofumi Niitsuma, Tooru Shimosegawa

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)202-209
Number of pages8
JournalVirology
Volume395
Issue number2
DOIs
Publication statusPublished - 2009 Dec 20

Keywords

  • A1762T/G1764A
  • Core promoter
  • G1862T
  • G1896A
  • HBV
  • HBcAg
  • Mutation
  • Precore
  • Replicative intermediates

ASJC Scopus subject areas

  • Virology

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