Evidence map›Paper›PMID 25521510›Full record

ArticlePLoS pathogens2014

HTLV-1 Tax-mediated inhibition of FOXO3a activity is critical for the persistence of terminally differentiated CD4+ T cells.

David Olagnier, Alexandre Sze, Samar Bel Hadj, Cindy Chiang, Courtney Steel, Xiaoying Han, Jean-Pierre Routy, Rongtuan Lin, John Hiscott, Julien van Grevenynghe

Open access · goldAbstract read
PubMed Full text at PMC Publisher
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 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.3field-weighted citation impact, top 43% 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

15 citing papers in PubMed, 20 citations in OpenAlex.

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  14. Molecular mechanisms of viral oncogenesis in humans.Nature reviews. Microbiology · 2018
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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

10 authors at 3 institutions in 2 countries.

David OlagnierLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada; VGTI Florida, Port St. Lucie, Florida, United States of America.
Alexandre SzeLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Samar Bel HadjLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Cindy ChiangVGTI Florida, Port St. Lucie, Florida, United States of America.
Courtney SteelVGTI Florida, Port St. Lucie, Florida, United States of America.
Xiaoying HanLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Jean-Pierre RoutyImmunodeficiency Service and Division of Haematology, Royal Victoria Hospital, McGill University Health Center, McGill University, Montreal, Quebec, Canada.
Rongtuan LinLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
John HiscottLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada; VGTI Florida, Port St. Lucie, Florida, United States of America.
Julien van GrevenyngheLady Davis Institute-Jewish General Hospital, McGill University, Montreal, Quebec, Canada; VGTI Florida, Port St. Lucie, Florida, United States of America.
McGill University · CAJewish General Hospital · CAVaccine & Gene Therapy Institute of Florida · US

Funding

Canadian Institutes of Health Research MOP-106686
6 · The paper itself

Abstract

The mechanisms involved in the persistence of activated CD4+ T lymphocytes following primary human T leukemia/lymphoma virus type 1 (HTLV-1) infection remain unclear. Here, we demonstrate that the HTLV-1 Tax oncoprotein modulates phosphorylation and transcriptional activity of the FOXO3a transcription factor, via upstream activation of the AKT pathway. De novo HTLV-1 infection of CD4+ T cells or direct lentiviral-mediated introduction of Tax led to AKT activation and AKT-dependent inactivation of FOXO3a, via phosphorylation of residues Ser253 and Thr32. Inhibition of FOXO3a signalling led to the long-term survival of a population of highly activated, terminally differentiated CD4+Tax+CD27negCCR7neg T cells that maintained the capacity to disseminate infectious HTLV-1. CD4+ T cell persistence was reversed by chemical inhibition of AKT activity, lentiviral-mediated expression of a dominant-negative form of FOXO3a or by specific small interfering RNA (siRNA)-mediated silencing of FOXO3a. Overall this study provides new mechanistic insight into the strategies used by HTLV-1 to increase long-term maintenance of Tax+CD4+ T lymphocytes during the early stages of HTLV-1 pathogenesis.

Indexed as

CD4-Positive T-LymphocytesCell DifferentiationCells, CulturedCell SurvivalForkhead Box Protein O3Forkhead Transcription FactorsGene Products, taxHTLV-I InfectionsHumansHuman T-lymphotropic virus 1Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA, Small InterferingSignal TransductionViral ProteinsForkhead Box Protein O3Forkhead Transcription FactorsFOXO3 protein, humanGene Products, taxPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA, Small InterferingViral Proteins

Identifiers

PMID25521510
PMCPMC4270795
OpenAlexW1994573769

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.