Evidence map›Paper›PMID 8970951›Full record

ArticleJournal of virology1996

Type, prevalence, and significance of core promoter/enhancer II mutations in hepatitis B viruses from immunosuppressed patients with severe liver disease.

S Günther, N Piwon, A Iwanska, R Schilling, H Meisel, H Will

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of virology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.

  1. Pooled it
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  16. Viral quasispecies evolution.Microbiology and molecular biology reviews : MMBR · 2012
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

S GüntherHeinrich-Pette-Institut für Experimentelle Virologie und Immunologie an der Universität Hamburg, Federal Republic of Germany.
N Piwon
A Iwanska
R Schilling
H Meisel
H Will
Leibniz Institute of Virology (LIV) · DEUniversität Hamburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Little is known about the functional significance of hepatitis B virus (HBV) sequence heterogeneity. Here we analyzed the type, frequency, and function of mutations in the core promoter/enhancer II region of HBV in immunosuppressed patients. The major HBV population in immunosuppressed patients with severe liver disease had deletions, insertions, and/or base changes in this region. Such mutations were not found in immunosuppressed patients with mild disease. Except for two mutations, all created a hepatocyte nuclear factor 1 (HNF1) binding site or a potential HNF3 binding site. Occasionally, known binding sites for C/EBP and HNF4 were additionally duplicated. Eleven mutated core promoter prototype sequences were functionally tested in the context of a wild-type genome by transfection in Huh7 cells. Despite the diversity of mutations tested, all decreased steady-state levels of pre-C mRNA drastically and increased those of the C mRNA/ pregenomic RNA. This correlated with reduced levels of secreted hepatitis B e antigen and increased intracellular levels of core and Pol proteins and replicative HBV DNA intermediates. The levels of secreted HBV DNA-containing particles were also increased although most of the mutations reduced the levels of pre-S/S mRNA and pre-S1, and pre-S2 proteins as well as secretion of hepatitis B surface antigen. These data reveal a novel class of HBV variants with HNF1 binding sites in the core promoter which are characterized by a defect in hepatitis B e antigen expression, enhanced replication, and altered protein levels, all probably mediated by altered transcription factor binding. The phenotype of these variants and their prevalence only in immunosuppressed patients with severe liver disease may indicate that they play a role in pathogenesis.

Indexed as

Enhancer Elements, GeneticPromoter Regions, GeneticAmino Acid SequenceBase SequenceBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsBinding SitesCCAAT-Enhancer-Binding ProteinsCulture MediaDNA-Binding ProteinsDNA, ViralGene Expression Regulation, ViralGenetic VariationHepatitis BHepatitis B Core AntigensHepatitis B Surface AntigensHepatitis B virusBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCCAAT-Enhancer-Binding ProteinsCulture MediaDNA-Binding ProteinsDNA, ViralHepatitis B Core AntigensHepatitis B Surface Antigenshepatitis B virus X proteinHepatocyte Nuclear Factor 1Hepatocyte Nuclear Factor 1-alphaHepatocyte Nuclear Factor 1-betaHepatocyte Nuclear Factor 4HNF1A protein, humanHNF1B protein, humanMLX protein, humanNuclear ProteinsPhosphoproteinsRNA PrecursorsTrans-ActivatorsTranscription FactorsViral Regulatory and Accessory Proteins

Identifiers

PMID8970951
PMCPMC190919
OpenAlexW1611884612

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.