Enhanced replication of hepatitis B virus with frameshift in the precore region found in fulminant hepatitis patients

Jun Inoue, Yoshiyuki Ueno, Yuta Wakui, Koji Fukushima, Yasuteru Kondo, Eiji Kakazu, Masashi Ninomiya, Hirofumi Niitsuma, Tooru Shimosegawa

研究成果: Article査読

26 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)1017-1025
ページ数9
ジャーナルJournal of Infectious Diseases
204
7
DOI
出版ステータスPublished - 2011 10 1

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 感染症

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