title: Enhanced replication of hepatitis B virus with frameshift in the precore region found in fulminant hepatitis patients.
abstract: BACKGROUND
  The genotype B of hepatitis B virus (HBV) was reported to associate with fulminant hepatitis (FH). We aimed to clarify the characteristics of HBV obtained from FH patients in an area of Japan where genotype B HBV is prevalent.
  
  
  METHODS
  Using serum samples of 16 HBV-associated FH patients, partial HBV sequences were determined. The effects of HBV mutation/insertion/deletion were evaluated using an in vitro HBV replication system.
  
  
  RESULTS
  Of the 16 HBV isolates, 31% belonged to subgenotype B1/Bj, 38% were subgenotype B2/Ba, and 31% were subgenotype C2/Ce. Notably, the single nucleotide insertion/deletion that resulted in a frameshift of the precore protein was found exclusively in 60% of B1/Bj strains. An in vitro study showed that all of the frameshift mutants had significantly higher amounts of HBV DNA than did the wild type. One of the isolates had a novel insertion of A between nucleotides 1900 and 1901, which resulted in a 3-nucleotide change within the Kozak sequence of the core protein and enhanced the core protein expression in vitro.
  
  
  CONCLUSIONS
  The frameshift insertion/deletion in the precore region enhanced HBV replication and might be associated with the development of FH by the subgenotype B1/Bj HBV.
authors: Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Jun
authors: J
authors: Inoue
authors: Yoshiyuki
authors: Y
authors: Ueno
authors: Yuta
authors: Y
authors: Wakui
authors: Koji
authors: K
authors: Fukushima
authors: Yasuteru
authors: Y
authors: Kondo
authors: Eiji
authors: E
authors: Kakazu
authors: Masashi
authors: M
authors: Ninomiya
authors: Hirofumi
authors: H
authors: Niitsuma
authors: Tooru
authors: T
authors: Shimosegawa
mesh_terms: D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D016368:Frameshift Mutation / Q000235:genetics*; D005838:Genotype; D056945:Hep G2 Cells; D006515:Hepatitis B virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007564:Japan; D017114:Liver Failure, Acute / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016254:Mutagenesis, Insertional / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D014758:Viral Core Proteins