The gene S promoter of hepatitis B virus confers constitutive gene expression

Malpiece, Yves; Michel, Marie‐Louise; Carloni, Guido; Revel, Michel; Tiollais, Pierre; Weissenbach, Jean

doi:10.1093/nar/11.13.4645

Cited by 24 publications

(17 citation statements)

References 39 publications

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“…In addition to the two transcripts detected in the infected liver, a minor transcript 4.2-4.5 kb in length was detected in cell line L154.HBV ( Figure IA, lane L154.HBV poly(A)+). Using highly sensitive assay conditions, Gough (1983) (Thomas, 1980) and hybridized with nick-translated plasmid pSHH2.1 (Cattaneo et Malpiece et al, 1983;Cattaneo et al, 1983a;Simonsen and Levinson, 1983). Nuclease digestion analysis was performed to discover if these signals were used in the infected liver (Berk and Sharp, 1978).…”

Section: Resultsmentioning

confidence: 99%

“…This suggests that the 5' ends of the 3.8-kb transcript are heterogeneous, because this transcript is present in the liver only at a slightly lower concentration than the 2.3-kb transcript, whose 5' ends were readily detected. Accordingly, no convincing homology to the TATA recognition sequence, precisely positioning transcription initiation (Corden et al, 1980) (Rail et al, 1983), in an SV40-HBV hybrid , and when used to express ,3-interferon (Malpiece et al, 1983). (b) The HBsAg transcript promoter, active in the infected liver and in rodent cell lines containing integrated HBV DNA (Cattaneo et al, 1983b;Standring et al, 1984).…”

Section: Resultsmentioning

confidence: 99%

“…In HBV-SV40 hybrids replicating to a high copy number in COS cells, spliced HBV RNAs were detected (Simonesen and Levinson, 1983;Cattaneo et al, 1983a). Finally, a promoter was mapped in three different heterologous systems Laub et al, 1983;Malpiece et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

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Hepatitis B virus transcription in the infected liver.

Cattaneo¹,

Will²,

Schaller³

1984

The EMBO Journal

167

110

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Hepatitis B virus (HBV) transcription was studied in the liver of an infected chimpanzee and compared with HBV transcription in heterologous systems. Besides the well characterized 2.3-kb surface antigen mRNA produced in most systems, a second major transcript was identified in the liver. This 3.8-kb transcript (-4300 bases) is slightly larger than the HBV genome and is probably involved both in core/e antigen synthesis and in HBV replication via reverse transcription. In addition, minor variants of the 2.3-kb surface antigen mRNA were characterzed as probably being involved in the expression of HBsAg-related minor proteins. Finally, several potential transcription signals, identified on the HBV genome using heterologous expression systems, were found to be poorly active if at all in the infected liver, thereby stressing the importance of HBV transcription studies performed with liver material.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Hepatitis B virus transcription in the infected liver.

Cattaneo¹,

Will²,

Schaller³

1984

The EMBO Journal

167

110

View full text Add to dashboard Cite

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“…These three proteins are encoded by the pre-S/S gene, which contains two promoters. The distal TATA-like promoter (SPI) transcribes a 2.4-kb mRNA for the synthesis of the large S protein, whereas the proximal simian virus 40-like promoter (SPII) transcribes a 2.1-kb mRNA for the synthesis of both the middle and the major S proteins (7,32,39).…”

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confidence: 99%

A liver-specific nuclear factor interacts with the promoter region of the large surface protein gene of human hepatitis B virus.

Chang¹,

Wang²,

Yuh³

et al. 1989

Mol. Cell. Biol.

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The outer envelope of the 42-nm virion of the human hepatitis B virus (HBV) is composed of the large, the middle, and the major surface proteins. Whereas the middle and the major surface proteins are transcribed from the SPIH promoter of the pre-S/S gene, the large surface protein is transcribed from the SPI promoter located upstream of SPIl. We liver-specific genes from human, mouse, and rat, with a consensus sequence (G/A)GTTA(A/C)TNNT(C/T) NNC(A/C). We further identified a nuclear factor present in the nuclear extracts of differentiated human hepatoma cell lines which interacted specifically with this element of the SPI promoter. This nuclear factor was similar to the rat liver-specific factor HNF-1, since an oligonucleotide containing the recognition sequence of HNF-1 could efficiently compete for the human factor in a footprinting assay. The sequence at nt -93 to -68 which was bound by this factor in SPI was termed the EINF-1-binding element. Activation of the SPI promoter by human differentiated hepatocyte nuclear factor 1, described in this report, probably explains, first, the formation of the 42-nm virion specifically in liver but not in several other tissues despite the synthesis of the middle and the major surface proteins in those tissues, and second, why only differentiated hepatoma cell lines are able to produce 42-nm-like virion particles on transfection by HBV DNA.Hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of hepatocellular carcinoma (4, 48). The virion has a diameter of approximately 42 nm with a 27-nm core enclosing a 3.2-kilobase (kb) partially single-stranded DNA genome (5, 49). The outer envelope of the virion is arrayed by three surface (S) proteins. The major S protein, 226 amino acids long, is encoded by the S region of the HBV genome; the middle S protein is encoded by the pre-S2 and S regions, with an additional 55 amino acids at the amino terminus of the major S protein; and the large S protein is encoded by the pre-Sl, pre-S2, and the S regions, with an additional 117 amino acids at the amino terminus of the middle S protein (25,38,47). These three proteins are encoded by the pre-S/S gene, which contains two promoters. The distal TATA-like promoter (SPI) transcribes a 2.4-kb mRNA for the synthesis of the large S protein, whereas the proximal simian virus 40-like promoter (SPII) transcribes a 2.1-kb mRNA for the synthesis of both the middle and the major S proteins (7, 32, 39).The major S protein can be produced from many different tissues in HBV-infected chimpanzees and in transgenic mice carrying HBV DNA (2,7,8,20). However, the large S protein is detected more specifically in liver and, in only a few cases in transgenic mice, in the kidney and heart. Furthermore, the time of appearance of the large S protein is coincident with the appearance of replicative intermediates of the viral genome (2,20). Together, these observations * Corresponding author. strongly indicate that expression of the large S protein gene is hepat...

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“…The 3.5-kb mRNA encodes viral polymerase and HBc/eAg and functions as the pregenome RNA for reverse transcription of the HBV genome as well (8,45,54,56). The 2.4-and 2.1-kb mRNAs are the templates for large and middle/major surface antigens, respectively (7,36,41,43), and the 0.8-kb mRNA is specific for X protein (42, 49). So far, two regions in the HBV genome have been shown to act as transcriptional enhancers.…”

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Identification of Multiple Transcription Factors, HLF, FTF, and E4BP4, Controlling Hepatitis B Virus Enhancer II

Ishida

Ueda²,

Ohkawa

et al. 2000

J Virol

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Hepatitis B virus (HBV) enhancer II (EnII) is a hepatotropic cis element which is responsible for the hepatocyte-specific gene expression of HBV. Multiple transcription factors have been demonstrated to interact with this region. In this study, the region from HBV nucleotides (nt) 1640 to 1663 in EnII was demonstrated to be essential for enhancer activity and to be another target sequence of putative transcription factors. To elucidate the factors which bind to this region, we used a yeast one-hybrid screening system and cloned three transcription factors, HLF, FTF, and E4BP4, from a human adult liver cDNA library. All of these factors had binding affinity to the sequence from nt 1640 to 1663. Investigation of the effects of these factors on transcriptional regulation revealed that HLF and FTF had stimulatory activity on nt 1640 to 1663, whereas E4BP4 had a suppressing effect. FTF coordinately activated both 3.5-kb RNA and 2.4/2.1-kb RNA transcription in a transient transfection assay with an HBV expression vector. HLF, however, activated only 3.5-kb RNA transcription, and in primer extension analysis, HLF strongly stimulated the synthesis of pregenome RNA compared to precore RNA. Thus, FTF stimulated the activity of the second enhancer, while HLF stimulated the activity of the core upstream regulatory sequence, which affects only the core promoter, and had a dominant effect on the pregenome RNA synthesis.Hepatitis B virus (HBV) causes acute and chronic hepatitis in humans, and chronic infection is closely associated with the development of hepatocellular carcinoma (3). HBV has a partially double-stranded 3.2-kb DNA genome containing four overlapping open reading frames (ORFs) encoding surface antigen (HBsAg), core/e antigen (HBc/eAg), polymerase, and X protein (19,47). Four promoters (CP, SPI, SPII, and XP) have been identified as cis regulators for transcription of the 3.5-, 2.4-, 2.1-, and 0.8-kb mRNAs, respectively. The 3.5-kb mRNA encodes viral polymerase and HBc/eAg and functions as the pregenome RNA for reverse transcription of the HBV genome as well (8,45,54,56). The 2.4-and 2.1-kb mRNAs are the templates for large and middle/major surface antigens, respectively (7,36,41,43), and the 0.8-kb mRNA is specific for X protein (42, 49). So far, two regions in the HBV genome have been shown to act as transcriptional enhancers. Enhancer I (EnI), which is located upstream of the X gene, displays a preference for hepatocytes (40, 48), while enhancer II (EnII), located just upstream of CP, shows highly restricted hepatocyte-specific activity (53, 57, 60); both enhancers stimulate transcription from the promoters (2,22,28,44,51,57,60). In transfection analysis with cloned HBV DNA, the 3.5-kb mRNAs were detected in well-differentiated human hepatoma cell lines but not in nonhepatic cells (9,46,50,55). This suggests that hepatocyte-specific factors are necessary for the transcription of pregenome RNA and that the hepatotropism of HBV replication might be attributable to the EnII function.EnII stimulates the transcript...

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The gene S promoter of hepatitis B virus confers constitutive gene expression

Cited by 24 publications

References 39 publications

Hepatitis B virus transcription in the infected liver.

Hepatitis B virus transcription in the infected liver.

A liver-specific nuclear factor interacts with the promoter region of the large surface protein gene of human hepatitis B virus.

Identification of Multiple Transcription Factors, HLF, FTF, and E4BP4, Controlling Hepatitis B Virus Enhancer II

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