Whole genome analysis of hepatitis B virus from four cases of fulminant hepatitis: Genetic variability and its potential role in disease pathogenicity

A. Alexopoulou, P. Karayiannis, S. J. Hadziyannis, J. Hou, J. Pickering, K. Luo, H. C. Thomas

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The precore stop-codon variant of hepatitis B virus (HBV) has been associated with fulminant hepatitis but is also found in patients with persistent infection and chronic hepatitis. We have examined the possibility that the severe outcome of infection in patients with fulminant disease may be a result of additional genomic variation. We sequenced the entire HBV genome from three patients of Greek and one patient of Chinese origin with fulminant hepatitis, and from two patients with hepatitis B e antigen (HBeAg) positive chronic infection from the same regions, using direct sequencing of amplified viral DNA. Three of the fulminant cases were infected with the precore stop-codon variant (HBeAg negative) and the fourth with the wild-type (HBeAg positive) virus. We compared sequences from our four fulminant isolates, and an additional fulminant isolate reported by others, with HBeAg positive carriers from the same regions and 12 published HBV genomes. There was a higher number of nucleotide and amino-acid substitutions throughout the HBV genome in the precore variant fulminant sequences than in the wild type. A cluster of mutations previously identified in the X region (126-132) in sequences reported in Japanese patients and encompassing the Enhancer II-Core Promoter region (1751-1768), were not found in our patients. We conclude that although there are no changes common to all sequences of HBV isolates from fulminant cases, some of these changes are in recognized cis-acting regulatory elements, whilst others are in the immediate vicinity of such elements. The effect of these mutations on viral genome transcription must now be determined.

Original languageEnglish
Pages (from-to)173-181
Number of pages9
JournalJournal of Viral Hepatitis
Volume3
Issue number4
Publication statusPublished - Jul 1996

Keywords

  • Fulminant hepatitis
  • Hepatitis B virus
  • Precore variants
  • Whole genome sequence

Fingerprint Dive into the research topics of 'Whole genome analysis of hepatitis B virus from four cases of fulminant hepatitis: Genetic variability and its potential role in disease pathogenicity'. Together they form a unique fingerprint.

  • Cite this