Genotype-dependent activation or repression of HBV enhancer II by transcription factor COUP-TF1

Fischer, Silke; Schmidt, Katja; Fiedler, Nicola; Glebe, Dieter; Schüttler, Christian G.; Sun, Jianguang; Gerlich, Wolfram H.; Repp, Reinald; Schaefer, Stephan

doi:10.3748/wjg.v12.i37.6054

Cited by 14 publications

(19 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rather, there was a change in band intensity depending on the mutations present, indicating either a more effective or reduced binding of the same factor(s). Such a suggestion is supported by recent findings showing differential binding of COUP-TF1 between different HBV genotypes (Fischer et al, 2006). Nevertheless, further experiments involving the use of nuclear cell extracts from other cell lines of hepatic origin (to strengthen the above results), as well as experiments to identify the transcription factor(s) involved in the binding, are warranted.…”

Section: Discussionmentioning

confidence: 59%

Effect of basal core promoter and pre-core mutations on hepatitis B virus replication

Jammeh

Tavner

Watson

et al. 2008

Journal of General Virology

108

View full text Add to dashboard Cite

There are two hypotheses explaining a fulminant outcome after hepatitis B virus (HBV) infection, both of which may be applicable at the same time: (i) basal core promoter (BCP) mutations increase viral replication, allowing rapid spread of the virus through the liver, and (ii) pre-core (pre-C) mutations abrogating hepatitis B e antigen (HBeAg) synthesis remove its tolerogenic effect, leading to a vigorous immune response. This study investigated the effect of these mutations on virus replication efficiency and HBeAg production. Substitutions A1762T/G1764A and T1753C, C1766T and T1768A in the BCP region, and G1896A and G1899A in the pre-C region, were examined either alone or in combination, using a common genetic background. Huh7 cells were transfected with these constructs and real-time PCR was used to quantify released virion-associated and intracellular HBV DNA, pregenomic RNA and pre-C mRNA. In addition, culture supernatants were tested for hepatitis B surface antigen (HBsAg) and HBeAg. The double BCP mutation (A1762T/G1764A) and the pre-C mutations (G1896A, G1899A), either alone or in combination, had no appreciable effect on the replication capacity of the virus. In contrast, clones with mutations at positions

show abstract

Section: Discussionmentioning

confidence: 59%

Effect of basal core promoter and pre-core mutations on hepatitis B virus replication

Jammeh

Tavner

Watson

et al. 2008

Journal of General Virology

108

View full text Add to dashboard Cite

show abstract

“…Thus, a certain combination of these modules would make up an HBV genotype. The findings of Fischer et al [74] are in support of this speculation. The authors described genotype specific activation or repression of HBV enhancer II, preCorepregenomic promoter by the transcription factor COUP-TF1.…”

Section: Figurementioning

confidence: 58%

Hepatitis B virus taxonomy and hepatitis B virus genotypes

Schaefer¹

2007

WJG

303

233

View full text Add to dashboard Cite

Hepatitis B virus (HBV) is a member of the hepadnavirus family. Hepadnaviruses can be found in both mammals (orthohepadnaviruses) and birds (avihepadnaviruses). The genetic variability of HBV is very high. There are eight genotypes of HBV and three clades of HBV isolates from apes that appear to be additional genotypes of HBV. Most genotypes are now divided into subgenotypes with distinct virological and epidemiological properties. In addition, recombination among HBV genotypes increases the variability of HBV. This review summarises current knowledge of the epidemiology of genetic variability in hepadnaviruses and, due to rapid progress in the field, updates several recent reviews on HBV genotypes and subgenotypes.

show abstract

“…Analysis of different HBV genomes in the GenBank database reveals that this sequence is well conserved among genotypes A, B, C, D, E, and G. Interestingly, the nucleotide sequences are somewhat different in genotypes F (5Ј-CGGTC AATGACCT-3Ј) and H (5Ј-CGGTCAACGACCT-3Ј) and present even higher homologies to the consensus FXRE. Differences in transcriptional regulation by COUP-TF1 have recently been reported to occur among HBV genotypes (9). Similarly, the influence of FXR␣ on different HBV strains could be further explored.…”

Section: Discussionmentioning

confidence: 98%

Transactivation of the Hepatitis B Virus Core Promoter by the Nuclear Receptor FXRα

Ramière

Scholtès

Diaz

et al. 2008

J Virol

View full text Add to dashboard Cite

Hepatitis B virus (HBV) core promoter activity is positively and negatively regulated by nuclear receptors, a superfamily of ligand-activated transcription factors, via cis-acting sequences located in the viral genome. In this study, we investigated the role of farnesoid X receptor alpha (FXR␣) in modulating transcription from the HBV core promoter. FXR␣ is a liver-enriched nuclear receptor activated by bile acids recognizing hormone response elements by forming heterodimers with retinoid X receptor alpha (RXR␣). Electrophoretic mobility shift assays demonstrated that FXR␣-RXR␣ heterodimers can bind two motifs on the HBV enhancer II and core promoter regions, presenting high homology to the consensus (AGGTCA) inverted repeat FXR␣ response elements. In transient transfection of the human hepatoma cell line Huh-7, bile acids enhanced the activity of a luciferase reporter containing the HBV enhancer II and core promoter sequences through FXR␣. Moreover, using a greater-than-genome-length HBV construct, we showed that FXR␣ also increased synthesis of the viral pregenomic RNA and DNA replication intermediates. The data strongly suggest that FXR␣ is another member of the nuclear receptor superfamily implicated in the regulation of HBV core promoter activity and that bile acids could play an important role in the natural history of HBV infection.Hepatitis B virus (HBV) infection is limited to hepatocytes of humans and primates and is associated with chronic hepatitis, cirrhosis, and hepatocellular carcinoma (10,19). HBV is an enveloped virus containing a 3.2-kb partially doublestranded DNA genome with four open reading frames. These open reading frames encode the reverse transcriptase, precore, and core proteins; three surface antigen proteins (pre-S1, pre-S2, and S); and the X protein. Regulation of HBV transcription is under the control of four promoters (the core, pre-S1, pre-S2/S, and X promoters) and two enhancer regions (EN1 and EN2). For some authors, the core promoter corresponds to two distinct promoters, namely the precore and pregenomic promoters (44,46). The core promoter activity, modulated by the EN2 region, plays a critical role in the virus life cycle. It initiates the synthesis of the precore and pregenomic 3.5-kb RNAs. The precore RNA encodes the precore protein, also called HBe antigen. The pregenomic RNA encodes both the polymerase and the core protein and serves as the template for viral DNA synthesis (24, 34).Multiple cellular transcription factor binding sites have been identified on these regulatory sequences (26,29,31,40,48,51), in particular for several nuclear receptors (NR) belonging to the superfamily of ligand-activated transcription factors (1,11,13,14,22,23). Two important NR response elements (NRRE), situated in the EN2 (NRRE enhII ) and the core promoter (NRRE pre-C ) regions, are recognized by hepatocyte nuclear factor 4 alpha (HNF4␣) and RXR␣-peroxisome proliferatoractivated receptor alpha (PPAR␣) heterodimers (13,30,44).In hepatoma cell lines, HNF4␣ and PPAR␣-RXR␣ upregulate synthes...

show abstract

Genotype-dependent activation or repression of HBV enhancer II by transcription factor COUP-TF1

Abstract: Regulation of transcription of the HBV genome seems to differ among HBV genomes derived from different genotypes. These differences in transcriptional control among HBV genotypes may be the molecular basis for differences in the clinical course among HBV genotypes.

Cited by 14 publications

References 32 publications

Effect of basal core promoter and pre-core mutations on hepatitis B virus replication

Effect of basal core promoter and pre-core mutations on hepatitis B virus replication

Hepatitis B virus taxonomy and hepatitis B virus genotypes

Transactivation of the Hepatitis B Virus Core Promoter by the Nuclear Receptor FXRα

Contact Info

Product

Resources

About