COMPLETE NUCLEOTIDE-SEQUENCES OF HEPATITIS-B VIRUS GENOMES ASSOCIATEDWITH EPIDEMIC FULMINANT-HEPATITIS

Pre-core/core mutants are frequently observed in patients with fulmina nt hepatitis. To investigate the extent of molecular characteristics o f hepatitis B virus (HBV) genomes implicated in the development of ful minant hepatitis, full-length HBV genomes were sequenced directly from sera of two patients with epidemic fatal fulminant hepatitis, after a mplification by the polymerase chain reaction. These two genomes, of 3 215 nucleotides, were 99.6% identical, indicating that a common source of HBV potentially caused fulminant hepatitis. Thirty unique nucleoti de mutations were commonly found in the two entire HBV genomes. Three were located in the stem-loop structure, changing this element to a mo re stable structure. Twenty-five unique amino acid substitutions were found in each open reading frame, except for the X and presurface 2 ge nes. One was located in the pre-surface 1 gene; two were in the surfac e gene; three were in the pre-core gene, including codons 28 (tryptoph an to stop codon) and 29 (glycine to aspartic acid); eight were in the core gene; and 11 were in the polymerase gene. The pre-core mutations at codons 28 and 29 were com mon to the two HBV strains reported prev iously in patients with epidemic fulminant hepatitis. Thus, HBV genome s associated with epidemic fatal fulminant hepatitis have numerous uni que mutations, located mainly in the polymerase gene, as well as the p re-core/core gene, including mutations in the stem-loop structure of t he pregenome encapsidation signal sequence. These mutations may be ass ociated with the development of fulminant hepatitis. (C) 1996 Wiley-Li ss, Inc.