Association between S21 substitution in the core protein of hepatitis B virus and fulminant hepatitis.
BACKGROUND
The viral factors of hepatitis B virus (HBV), such as genotypes and mutations, were reported to affect the development of fulminant hepatitis B (FHB), but the mechanism is still unclear.


OBJECTIVE
To investigate HBV mutations associated with FHB, especially in the subgenotype B1/Bj HBV (HBV/B1), which are known to cause FHB frequently in Japan.


METHODS
A total of 96 serum samples from acute self-limited hepatitis B (AHB) patients and 13 samples from FHB patients were used for full-genome/partial sequencing. A total of 107 chronic infection patients with HBV were also examined for the distribution of mutants.


RESULTS
In the analysis of full-genome sequences of HBV/B1 (FHB, n=11; non-FHB, n=35) including those from the databases, mutations at nt 1961 [T1961V (not T)] and nt 1962 [C1962D (not C)], which change S21 in the core protein, were found more frequently in FHB than in non-FHB (100% vs. 20%, 55% vs. 3%, respectively). When our FHB and AHB samples were compared, T1961V and C1962D were significantly more frequent in FHB than in AHB, both in the overall analysis (46% vs. 6%, 39% vs. 3%, respectively) and in HBV/B1 (100% vs. 29%, 100% vs. 14%, respectively). A newly developed PCR system detecting T1961V showed that HBV/B1 and low viral load were independent factors for the mutation among chronic infection patients.


CONCLUSIONS
T1961V/C1962D mutations were found frequently in FHB, especially in HBV/B1. The resulting S21 substitution in the core protein may play important roles in the development of FHB.
Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Jun
J
Inoue
Yoshiyuki
Y
Ueno
Kaori
K
Kawamura
Takeshi
T
Yamamoto
Yutaka
Y
Mano
Masahito
M
Miura
Tomoo
T
Kobayashi
Hirofumi
H
Niitsuma
Yasuteru
Y
Kondo
Eiji
E
Kakazu
Masashi
M
Ninomiya
Osamu
O
Kimura
Noriyuki
N
Obara
Naoki
N
Kawagishi
Yoshitaka
Y
Kinouchi
Tooru
T
Shimosegawa
D000328:Adult; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000473:pathology* / Q000821:virology*; D006512:Hepatitis B Core Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000235:genetics; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D050505:Mutant Proteins