Functional analysis of HBV genomes from patients with fulminant hepatitis

被引:48
作者
Sterneck, M
Kalinina, T
Günther, S
Fischer, L
Santantonio, T
Greten, H
Will, H
机构
[1] Univ Hamburg, Krankenhaus Eppendorf, Med Klin & Poliklin, Dept Med, D-20246 Hamburg, Germany
[2] Univ Hamburg, Krankenhaus Eppendorf, Dept Surg, D-20246 Hamburg, Germany
[3] Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-2000 Hamburg, Germany
[4] Inst Virol, Moscow, Russia
[5] Clin Malattie Infett, Bari, Italy
关键词
D O I
10.1002/hep.510280530
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Two previous case reports suggest that hepatitis B virus (HBV) core promoter variants with a high replication competence contribute to the pathogenesis of fulminant hepatitis B (FHB). We recently found in HBV genomes from patients with FHB an accumulation of mutations within the core promoter region. Therefore, the aim of this study was to investigate the phenotype of these HBV variants. Replication competence and expression of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) of viral genomes from seven patients with FHB and one patient with fulminant recurrent hepatitis after liver transplantation were analyzed by transfection experiments in human hepatoma cells. Compared with wild-type virus, the HBV variants from the seven patients with FHB produced similar or slightly lower levels of intracellular replicative intermediates and extracellular viral particles. In contrast, the HBV genomes from the patient with fulminant recurrent hepatitis synthesized and secreted significantly more HBV DNA. All genomes tested expressed similar or even higher levels of HBeAg compared with wild-type virus, except for those from four patients with a precore stop codon mutation in the respective dominant viral populations. The level of HBsAg produced by all variant genomes was similar or reduced compared with wild-type virus. These data indicate that in some cases HBV variants with enhanced replication competence and/or a defect in HBeAg expression may contribute to the development of FHB. However, neither phenotype is an essential prerequisite; thus, an additional role of other viral or host factors in the pathogenesis of FI-IB is suggested.
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页码:1390 / 1397
页数:8
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