Repression of enhancer II activity by a negative regulatory element in the hepatitis B virus genome

Lo, Wei-Yu; Ting, Ling-Pai

doi:10.1128/jvi.68.3.1758-1764.1994

Cited by 37 publications

(20 citation statements)

References 31 publications

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“…The X region is reported to be necessary for the production of infectious progeny virus in susceptible hosts from experiments in vivo using X gene mutants of woodchuck hepatitis virus (WHV) (4,39). The X region contains many important elements for HBV proliferation including the core promoter (38), a negative regulatory element that abolishes the function of the core promoter (11) and enhancer II (36,37). DR1 and DR2, which are implicated in the origin of HBV DNA, are also located in the X region (25).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus with X Gene Mutation Is Associated with the Majority of Serologically “Silent” Non‐B, Non‐C Chronic Hepatitis

Fukuda

Ishimura

Kushiyama

et al. 1996

Microbiology and Immunology

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Hepatitis B virus (HBV) with X gene mutations has been a putative pathogen of chronic hepatitis without serological markers of known hepatitis viruses. The aim of this study was to reconfirm whether the HBV with the X gene mutation is associated with these serologically "silent" non-B, non-C (NBNC) chronic hepatitis, alcoholic liver disease (ALD) and autoimmune hepatitis (AIH). HBV DNA was amplified from serum and sequenced in 30 patients with NBNC chronic hepatitis in comparison with 20 patients with ALD and 5 patients with AIH. HBV DNA was identified in 21 patients (70%) in NBNC chronic hepatitis by nested polymerase chain reaction while only one patient (5%) in ALD and none in AIH showed HBV DNA. Eighteen (85.7%) of the 21 identified HBV DNAs had an identical 8-nucleotide deletion mutation at the distal part of the X region. This mutation affected the core promoter and the enhancer II sequence of HBV DNA and created a translational stop codon which truncated the X protein by 20 amino acids from the Cterminal end. All the HBV DNAs had a precore mutation at the 83rd nucleotide resulting in disruption of HBe antigen synthesis. These results indicate that HBV mutants are closely associated with the majority of serologically "silent" NBNC chronic hepatitis cases and the population of such mutant HBV DNAs is not uniform.

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Section: Discussionmentioning

confidence: 99%

Hepatitis B Virus with X Gene Mutation Is Associated with the Majority of Serologically “Silent” Non‐B, Non‐C Chronic Hepatitis

Fukuda

Ishimura

Kushiyama

et al. 1996

Microbiology and Immunology

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“…The CURS can be subdivided into unitary sequence motifs that positively regulate BCP activity, namely: α (nts 1646-1668), γ (nts 1671-1686) and δ (nts 1687-1703), whereas β (nts 1704-1714) regulates negatively [26]. The minimal sequence of ENII has variously been defined as nts 1687-1805 [39], nts 1627-1732 [9], nts 1685-1774 [11] and nts 1646-1741 [41]. ENII is composed of two interacting sequence motifs, a 23-bp box α (nt 1646-1668) and a 12-bp box β (nt 1704-1725) [12].…”

Section: The Basic Core Promotermentioning

confidence: 99%

“…ENII. The minimum sequence for enhancer activity has variously been defined at nts 1687-1805 [39], nts 1627-1732 [9], nts 1685-1774 [11] and nts 1646-1741 [41]. ENII is composed of two interacting sequence motifs: a 23-bp box α (nts 1646-1668) and a 12-bp box β (nts 1704-1725) [12] (Fig.…”

Section: The Upstream Regulatory Regionmentioning

confidence: 99%

“…It can stimulate the S and X promoters from a downstream position. Alternatively, the same sequence can also function as a CURS that activates the CP in a position-and orientation-dependent manner [12,40,41].…”

Section: The Upstream Regulatory Regionmentioning

confidence: 99%

“…The NRE (nts 1613-1636), upstream of ENII, can repress both ENII and CURS in differentiated liver cells. The NRE has a minor inhibitory effect on its own but is strongly repressive in the presence of a functional ENII [41]. The NRE is composed of at least three different subregions: NRE-α, NRE-β and NRE-γ.…”

Section: The Upstream Regulatory Regionmentioning

confidence: 99%

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The core promoter of hepatitis B virus

Kramvis

Kew

1999

Journal of Viral Hepatitis

130

114

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The core promoter (CP) of hepatitis B virus (HBV) plays a central role in HBV replication and morphogenesis, directing the transcription of both species of 3.5 kb mRNA: pregenomic (pg) RNA and precore (pre-C) mRNA. The CP overlaps the 3' end of the X open-reading frame (ORF) and the 5' end of the pre-C/C ORF. The major functional elements of the CP are the upper regulatory region (URR) and the basic core promoter (BCP). The BCP is sufficient for accurate initiation of both pre-C mRNA and pgRNA transcription. It contains four AT-rich regions and the initiators for pre-C mRNA and pgRNA transcription. The upstream regulatory region consists of the negative regulatory element and the core upstream regulatory sequence. Co-operative interaction of various liver-enriched and ubiquitous transcription factors is necessary for liver-specific expression from the CP. These factors bind to the CP. Sequence conservation within the CP is crucial for maintaining active viral replication, and variation may contribute to the persistence of HBV within the host, leading to chronic infection and, ultimately, hepatocarcinogenesis. The most frequently described mutations within this region are an A to T transversion at position 1762 together with a G to A transition at position 1764. This double mutant is accompanied by a reduced level of hepatitis B e antigen (HBeAg) expression. Deletions, insertions and duplications occur within the CP.

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Major Differences between WHV and HBV in the Regulation of Transcription

Summers

Burch

et al. 1997

Virology

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Studies were carried out to further characterize enhancer and promoter elements on the woodchuck hepatitis virus (WHV) genome. We were able to confirm the existence of WHV promoters analogous to the major promoters of the related human hepatitis B virus (HBV) and of an enhancer analogous to the recently described WHV E2 element (Ueda, K., Wei, Y., and Ganem, D., Virology 217, 413, 1996). However, we were unable to identity an enhancer analogous to the E1 element of (HBV), despite the fact that these two viruses share a high degree of sequence homology and genetic organization. Some factor binding sites in the E1 region appeared to be conserved between the two viruses and may be required for the activity of the overlapping X gene promoter of WHV. Others did not appear to be essential for WHV X gene promoter activity, and their functional activity, if any, was not revealed. Our failure to detect a functional enhancer element in the region of WHV homologous to the HBV E1 enhancer may indicate that (i) fundamental differences exist in transcriptional regulation of the small circular genomes of WHV and HBV; (ii) WHV contains an E1 element which is functional in the context of the intact viral genome, but which is unable to function in the context of the various expression constructs used in our experiments; or (iii) correct regulation of WHV transcription via an E1 element is dependent upon transcription factors which are not expressed in the liver-specific cell lines used in our experiments.

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Repression of enhancer II activity by a negative regulatory element in the hepatitis B virus genome

Cited by 37 publications

References 31 publications

Hepatitis B Virus with X Gene Mutation Is Associated with the Majority of Serologically “Silent” Non‐B, Non‐C Chronic Hepatitis

Hepatitis B Virus with X Gene Mutation Is Associated with the Majority of Serologically “Silent” Non‐B, Non‐C Chronic Hepatitis

The core promoter of hepatitis B virus

Major Differences between WHV and HBV in the Regulation of Transcription

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