Evidence map›Paper›PMID 25166506›Full record

ArticlePLoS pathogens2014

A locus encompassing the Epstein-Barr virus bglf4 kinase regulates expression of genes encoding viral structural proteins.

Ayman El-Guindy, Francesc Lopez-Giraldez, Henri-Jacques Delecluse, Jessica McKenzie, George Miller

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

31 citing papers in PubMed, 36 citations in OpenAlex.

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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

5 authors at 2 institutions in 2 countries.

Ayman El-GuindyDepartment of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Francesc Lopez-GiraldezYale Center for Genome Analysis (YCGA), Yale University, West Haven, Connecticut, United States of America.
Henri-Jacques DelecluseDepartment of Tumor Virology, German Cancer Research Center, Im Neuenheimer Feld, Heidelberg, Germany.
Jessica McKenzieDepartment of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America.
George MillerDepartment of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut, United States of America; Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut, United States of America.
Yale University · USHeidelberg University · DE

Funding

Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI DAVID L RIMM · 1985 to 2026
$85.0M
VIRAL SMALL RNPS--ROLES IN CELL TRANSFORMATIONP01CA016038 · NCI · YALE UNIVERSITY · PI DIMAIO, DANIEL C. · 1985 to 2020
$25.6M
STUDIES OF EPSTEIN-BARR VIRUSR37CA012055 · NCI · YALE UNIVERSITY · PI MILLER, I. GEORGE · 1989 to 2012
$4.4M
STUDIES OF EPSTEIN-BARR VIRUSR01CA012055 · NCI · YALE UNIVERSITY · PI MILLER, I. GEORGE · 1985 to 2002
$737k
NCI NIH HHS P01 CA016038NCI NIH HHS P30 CA016359NCI NIH HHS R01 CA012055NCI NIH HHS R37 CA012055
6 · The paper itself

Abstract

The mechanism regulating expression of late genes, encoding viral structural components, is an unresolved problem in the biology of DNA tumor viruses. Here we show that BGLF4, the only protein kinase encoded by Epstein-Barr virus (EBV), controls expression of late genes independent of its effect on viral DNA replication. Ectopic expression of BGLF4 in cells lacking the kinase gene stimulated the transcript levels of six late genes by 8- to 10-fold. Introduction of a BGLF4 mutant that eliminated its kinase activity did not stimulate late gene expression. In cells infected with wild-type EBV, siRNA to BGLF4 (siG4) markedly reduced late gene expression without compromising viral DNA replication. Synthesis of late products was restored upon expression of a form of BGLF4 resistant to the siRNA. Studying the EBV transcriptome using mRNA-seq during the late phase of the lytic cycle in the absence and presence of siG4 showed that BGLF4 controlled expression of 31 late genes. Analysis of the EBV transcriptome identified BGLF3 as a gene whose expression was reduced as a result of silencing BGLF4. Knockdown of BGLF3 markedly reduced late gene expression but had no effect on viral DNA replication or expression of BGLF4. Our findings reveal the presence of a late control locus encompassing BGLF3 and BGLF4 in the EBV genome, and provide evidence for the importance of both proteins in post-replication events that are necessary for expression of late genes.

Indexed as

Blotting, NorthernGene Expression Regulation, ViralGenetic LociHEK293 CellsHumansProtein Serine-Threonine KinasesReal-Time Polymerase Chain ReactionTransfectionViral ProteinsViral Structural ProteinsVirus ReplicationBGLF4 protein, Epstein-Barr virusProtein Serine-Threonine KinasesViral ProteinsViral Structural Proteins

Identifiers

PMID25166506
PMCPMC4148442
OpenAlexW2014736425

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.