Evidence map›Paper›PMID 26654401›Full record

ArticleAutophagy2016

Analysis of the role of autophagy inhibition by two complementary human cytomegalovirus BECN1/Beclin 1-binding proteins.

Lina Mouna, Eva Hernandez, Dorine Bonte, Rebekka Brost, Larbi Amazit, Laura R Delgui, Wolfram Brune, Adam P Geballe, Isabelle Beau, Audrey Esclatine

Open access · bronzeAbstract read
In one paragraph

Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

66 citing papers in PubMed, 99 citations in OpenAlex.

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  14. Viruses and autophagy: bend, but don't break.Nature reviews. Microbiology · 2024
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6 more citing papers are in PubMed but not listed here.

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

10 authors at 8 institutions in 4 countries.

Lina Mounaa Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay , Gif sur Yvette , France.
Eva Hernandeza Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay , Gif sur Yvette , France.
Dorine Bonteb CNRS UMR8200, Univ Paris-Sud, Institut Gustave Roussy , Villejuif , France.
Rebekka Brostc Heinrich Pette Institute, Leibniz Institute for Experimental Virology , Hamburg , Germany.
Larbi Amazitd INSERM UMR-S-1185, Faculty of Medicine , Univ Paris-Sud , Le Kremlin Bicêtre , France.
Laura R Delguie Instituto de Histología y Embriología (IHEM), Universidad Nacional de Cuyo-CONICET , Mendoza , Argentina.
Wolfram Brunec Heinrich Pette Institute, Leibniz Institute for Experimental Virology , Hamburg , Germany.
Adam P Geballef Fred Hutchinson Cancer Research Center and University of Washington , Seattle , WA , USA.
Isabelle Beaud INSERM UMR-S-1185, Faculty of Medicine , Univ Paris-Sud , Le Kremlin Bicêtre , France.
Audrey Esclatinea Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ Paris-Sud, Université Paris-Saclay , Gif sur Yvette , France.
Centre National de la Recherche Scientifique · FRLeibniz Institute of Virology (LIV) · DEFred Hutch Cancer Center · USInserm · FRInstitut Gustave Roussy · FRUniversidad Nacional de Cuyo · ARUniversité Paris-Saclay · FRUniversité Paris-Sud · FR

Funding

TRANSLATIONAL CONTROL OF CYTOMEGALOVIRUS GENE EXPRESSIONR01AI026672 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEBALLE, ADAM P. · 1994 to 2017
$6.9M
TRANSLATIONAL CONTROL OF CYTOMEGALOVIRUS GENE EXPRESSIONR29AI026672 · NIAID · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GEBALLE, ADAM P. · 1988 to 1992
–
NIAID NIH HHS AI026672NIAID NIH HHS R01 AI026672
6 · The paper itself

Abstract

Autophagy is activated early after human cytomegalovirus (HCMV) infection but, later on, the virus blocks autophagy. Here we characterized 2 HCMV proteins, TRS1 and IRS1, which inhibit autophagy during infection. Expression of either TRS1 or IRS1 was able to block autophagy in different cell lines, independently of the EIF2S1 kinase, EIF2AK2/PKR. Instead, TRS1 and IRS1 interacted with the autophagy protein BECN1/Beclin 1. We mapped the BECN1-binding domain (BBD) of IRS1 and TRS1 and found it to be essential for autophagy inhibition. Mutant viruses that express only IRS1 or TRS1 partially controlled autophagy, whereas a double mutant virus expressing neither protein stimulated autophagy. A mutant virus that did not express IRS1 and expressed a truncated form of TRS1 in which the BBD was deleted, failed to control autophagy. However, this mutant virus had similar replication kinetics as wild-type virus, suggesting that autophagy inhibition is not critical for viral replication. In fact, using pharmacological modulators of autophagy and inhibition of autophagy by shRNA knockdown, we discovered that stimulating autophagy enhanced viral replication. Conversely, inhibiting autophagy decreased HCMV infection. Thus, our results demonstrate a new proviral role of autophagy for a DNA virus.

Indexed as

AutophagyBeclin-1CytomegalovirusCytomegalovirus InfectionseIF-2 KinaseHeLa CellsHumansMaleMutationProtein BindingProtein DomainsRecombination, GeneticViral ProteinsBeclin-1BECN1 protein, humanEIF2AK2 protein, humaneIF-2 KinaseTRS1 protein, Human herpesvirus 5Viral ProteinsautophagyBECN1cytomegalovirusEIF2AK2/PKRIRS1TRS1

Identifiers

PMID26654401
PMCPMC4836022
OpenAlexW2202812349

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.