Evidence map›Paper›PMID 21814558›Full record

ArticlePloS one2011

The G1613A mutation in the HBV genome affects HBeAg expression and viral replication through altered core promoter activity.

Man-Shan Li, Terrence Chi-Kong Lau, Sophie Ka-Ping Chan, Chi-Hang Wong, Patrick Kwok-Shing Ng, Joseph Jao-Yiu Sung, Henry Lik-Yuen Chan, Stephen Kwok-Wing Tsui

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 18% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Viruses · 2020
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  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. X protein mutations in hepatitis B virus DNA predict postoperative survival in hepatocellular carcinoma.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014
    Article
  12. Review
  13. Article
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

8 authors at 2 institutions in 2 countries.

Man-Shan LiSchool of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR, China.
Terrence Chi-Kong Lau
Sophie Ka-Ping Chan
Chi-Hang Wong
Patrick Kwok-Shing Ng
Joseph Jao-Yiu Sung
Henry Lik-Yuen Chan
Stephen Kwok-Wing Tsui
Chinese University of Hong Kong · CNCity University of Hong Kong · HK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Infection of hepatitis B virus (HBV) causes acute and chronic hepatitis and is closely associated with the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we demonstrated that the G1613A mutation in the HBV negative regulatory element (NRE) is a hotspot mutation in HCC patients. In this study, we further investigated the functional consequences of this mutation in the context of the full length HBV genome and its replication. We showed that the G1613A mutation significantly suppresses the secretion of e antigen (HBeAg) and enhances the synthesis of viral DNA, which is in consistence to our clinical result that the G1613A mutation associates with high viral load in chronic HBV carriers. To further investigate the molecular mechanism of the mutation, we performed the electrophoretic mobility shift assay with the recombinant RFX1 protein, a trans-activator that was shown to interact with the NRE of HBV. Intriguingly, RFX1 binds to the G1613A mutant with higher affinity than the wild-type sequence, indicating that the mutation possesses the trans-activating effect to the core promoter via NRE. The trans-activating effect was further validated by the enhancement of the core promoter activity after overexpression of RFX1 in liver cell line. In summary, our results suggest the functional consequences of the hotspot G1613A mutation found in HBV. We also provide a possible molecular mechanism of this hotspot mutation to the increased viral load of HBV carriers, which increases the risk to HCC.

Indexed as

Gene Expression Regulation, ViralGenome, ViralBlotting, NorthernBlotting, SouthernBlotting, WesternCarcinoma, HepatocellularDNA-Binding ProteinsDNA, ViralElectrophoretic Mobility Shift AssayEnzyme-Linked Immunosorbent AssayFemaleHepatitis B, ChronicHepatitis B e AntigensHepatitis B Surface AntigensHepatitis B virusHumansDNA-Binding ProteinsDNA, ViralHepatitis B e AntigensHepatitis B Surface AntigensLuciferasesRegulatory Factor X1Regulatory Factor X Transcription FactorsRFX1 protein, humanTrans-ActivatorsTranscription Factors

Identifiers

PMID21814558
PMCPMC3140978
OpenAlexW2019075278

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.