The hepatitis B virus

Tiollais, Pierre; Pourcel, Christine; Dejean, Anne

doi:10.1038/317489a0

Cited by 1,144 publications

(475 citation statements)

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“…OM1 is a point mutant of p53, where Glu was replaced by Gly (aa 266) (Sakai and Tsuchida, 1992). A mutant p53, p53d(346 ± 393), has lost the C-terminal region from aa 346 to the C-terminus (Tsutsumi-Ishii et al, 1995).…”

Section: Plasmid Dnamentioning

confidence: 99%

“…Hepatitis B virus (HBV) is closely related not only to acute or chronic hepatitis, but also to the development of hepatocellular carcinoma (HCC) (for review, see Ganem and Varmus, 1987;Tiollais et al, 1985). One of the HBV genes X, codes a basic protein of 154 amino acids, which has been implicated in the carcinogenicity of this virus as a potential causative factor because of its ability to induce transformation of rodent cells (Hohne et al, 1990;Rakotomahanina et al, 1994;Shirakata et al, 1989) and to cause development of HCC in transgenic mice (Kim et al, 1991).…”

Section: Introductionmentioning

confidence: 99%

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Cytoplasmic retention of the p53 tumor suppressor gene product is observed in the hepatitis B virus X gene-transfected cells

et al. 1997

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It has been suggested that hepatitis B virus (HBV) X gene activates X gene expression by disrupting the function of p53 tumor suppressor gene (Takada et al., 1996). To ®nd out their connection, eect of X protein expression on the nuclear localization of p53 protein in human hepatoma cells was examined by the immunouorescent double-staining technique. The location of transiently-expressed p53 protein was examined in X gene-transfected cells, where X protein was detected in the cytoplasm. The nuclear location of transientlyexpressed p53 protein was changed to the cytoplasm by X protein co-expression. Endogenous p53 protein was also observed in the cytoplasm by X protein expression. The transcriptional activation domain of X protein and the carboxy-terminal region of p53 protein were found mutually responsible for the cytoplasmic retention of p53 protein in X gene-transfected cells. Therefore, the cytoplasmic retention of p53 protein may be closely correlated to the function of X protein expressed in transfected cells.

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Section: Plasmid Dnamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytoplasmic retention of the p53 tumor suppressor gene product is observed in the hepatitis B virus X gene-transfected cells

et al. 1997

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“…The viral genome can integrate into patients' liver cell chromosomes, and a significant fraction of such patients later develop hepatocellular carcinoma (1). Therefore, studies with this virus on the mechanism of regulation of gene expression and replication are of substantial importance in virology as well as in public health.…”

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confidence: 99%

Stable expression and replication of hepatitis B virus genome in an integrated state in a human hepatoma cell line transfected with the cloned viral DNA.

Tsurimoto¹,

Fujiyama²,

Matsubara³

1987

Proc. Natl. Acad. Sci. U.S.A.

182

120

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A human hepatocellular carcinoma cell line (Huh6-c15) was transfected with a recombinant DNA molecule that consists of tandemly arranged hepatitis B virus (HBV) genome and a neomycin-resistant gene. One done resistant to G-418 produces and releases surface antigen and e antigen into medium at a high level and accumulates core particles intracellularly. This clone has a chromosomally integrated set of the original recombinant DNA and produces a 3.5-kilobase transcript corresponding to the pregenome RNA as well as HBV DNAs in an extrachromosomal form. Most of these DNAs were in single-stranded or partially double-stranded form and were packaged in the intracellular core particles. In the medium, particles were detected that contained HBV DNA and were morphologically indistinguishable from Dane particles. These results demonstrate that the HBV genome in an integrated state acted as a template for viral gene expression and replication. The cells were maintained for more than 6 months without losing the ability to produce the extrachromosomal HBV DNA and Dane-like particles. Thus, the cells can be used as a model system for analyses of gene expression and DNA replication of HBV in human hepatocytes.

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“…Hepatitis B virus (HBV) 1 is a small virus with a 3.2-kb partially double-stranded DNA genome, containing four open reading frames: the surface antigen, the core antigen, the polymerase, and the X protein (1,2). HBV is a major pathogen causing acute and chronic liver diseases, such as cirrhosis and hepatocellular carcinoma (3,4).…”

mentioning

confidence: 99%

Suppression of Hepatitis B Virus Core Promoter by the Nuclear Orphan Receptor TR4

Lin

Lee

et al. 2003

Journal of Biological Chemistry

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The TR4 orphan receptor is a member of the nuclear receptor superfamily that modulates gene expression via binding to the AGGTCA direct repeat hormone response element. Here we report a functional study of TR4 interaction with the core promoter of the hepatitis B virus (HBV). The electrophoretic mobility shift assay shows that TR4 can bind to the direct repeat 1 sequence element (AGGTTAAAGGTCT, nucleotide coordinates 1757-1769, TR4RE-HBV) on the HBV core promoter. TR4 also can enhance the activity of a synthetic luciferase reporter linked with four copies of TR4RE-HBV in either liver HepG2 or non-liver H1299 cells in a dose-dependent manner. Surprisingly, TR4 represses the activity of a luciferase reporter containing the entire HBV genome sequences. Moreover, mutation of this TR4RE-HBV site in the HBV core promoter diminishes the TR4 suppression effect. This TR4-induced suppression of HBV core promoter activity is further confirmed by primer extension analysis of the HBV core RNAs, showing that TR4 represses both pre-core and core mRNAs. Further dissection of this repressive mechanism indicates that TR4 may suppress the HBV core promoter activity via repressing HNF4␣-mediated transactivation by protein-protein interactions without inhibition of HNF4␣ DNA binding. Furthermore, our results indicate that the N-and C-terminal regions of TR4 protein are required for TR4-HNF4␣ interaction. It is possible that TR4-HNF4␣ interaction may block the HNF4␣ function that results in the suppression of HBV gene expression. Together, these results demonstrate that TR4 can serve as a negative modulator in the transcriptional regulation of HBV core gene expression.Hepatitis B virus (HBV) 1 is a small virus with a 3.2-kb partially double-stranded DNA genome, containing four open reading frames: the surface antigen, the core antigen, the polymerase, and the X protein (1, 2). HBV is a major pathogen causing acute and chronic liver diseases, such as cirrhosis and hepatocellular carcinoma (3, 4). HBV transcripts are regulated by the transcriptional control of four different promoters and two enhancer elements (5). HBV is replicated from a RNA intermediate as a template for reverse transcription (1). The core promoter controls the expression of the 3.5-kb core mRNA (C mRNA) as the template for replication, and the expression of the pre-core mRNA (pre-C mRNA) for the translation of the HBeAg precursor (6). Recently, multiple binding sites for liverspecific or ubiquitous transcription factors and several hormone response elements (HRE) have been identified in the core promoter region, including Sp1 (7, 8), TATA-binding protein (9), HNF3 (10), HNF4␣ (11), C/EBP (12), and other members of the nuclear receptor superfamily, such as the retinoid X receptor (RXR␣), peroxisome proliferator-activated receptor (PPAR␣), COUP-TF1, and ARP1 (13). For example, HNF4␣ and RXR␣/PPAR␣ can stimulate the expression of the 3.5-kb core RNA, COUP-TF1 suppresses the expression of both the pre-C RNA and C RNA, and TR2 preferentially represses the expression of ...

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The hepatitis B virus

Cited by 1,144 publications

References 95 publications

Cytoplasmic retention of the p53 tumor suppressor gene product is observed in the hepatitis B virus X gene-transfected cells

Cytoplasmic retention of the p53 tumor suppressor gene product is observed in the hepatitis B virus X gene-transfected cells

Stable expression and replication of hepatitis B virus genome in an integrated state in a human hepatoma cell line transfected with the cloned viral DNA.

Suppression of Hepatitis B Virus Core Promoter by the Nuclear Orphan Receptor TR4

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