TY - JOUR
T1 - Enhanced replication of hepatitis B virus with frameshift in the precore region found in fulminant hepatitis patients
AU - Inoue, Jun
AU - Ueno, Yoshiyuki
AU - Wakui, Yuta
AU - Fukushima, Koji
AU - Kondo, Yasuteru
AU - Kakazu, Eiji
AU - Ninomiya, Masashi
AU - Niitsuma, Hirofumi
AU - Shimosegawa, Tooru
N1 - Funding Information:
This work was supported in part by a Grant-in-Aid for Young Scientists (B) (22790627) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and grants from the Ministry of Health, Labor, and Welfare of Japan.
PY - 2011/10/1
Y1 - 2011/10/1
N2 - 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.
AB - 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.
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U2 - 10.1093/infdis/jir485
DO - 10.1093/infdis/jir485
M3 - Article
C2 - 21881116
AN - SCOPUS:80052416557
SN - 0022-1899
VL - 204
SP - 1017
EP - 1025
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 7
ER -
