Enhanced Replication of Hepatitis B Virus With Frameshift in the Precore Region Found in Fulminant Hepatitis Patients

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http://jid.oxfordjournals.org/content/204/7/1017.abstract?etoc

Journal of Infectious Diseases

Volume204, Issue7

Pp. 1017-1025.

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 and

Tooru Shimosegawa

+ Author Affiliations

Division of Gastroenterology, Tohoku University Graduate School of Medicine,

Sendai, Japan

Correspondence: Yoshiyuki Ueno, MD, PhD, Division of Gastroenterology, Tohoku

University Graduate School of Medicine, 1-1 Seiryo, Aoba-ku, Sendai 980-8574,

Japan (yueno@...).

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.

Received January 14, 2011.

Accepted May 26, 2011.

© The Author 2011. Published by Oxford University Press on behalf of the

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