Evidence map›Paper›PMID 23221426›Full record

ArticleAIDS (London, England)2013

Suberoylanilide hydroxamic acid induces limited changes in the transcriptome of primary CD4(+) T cells.

Nadejda Beliakova-Bethell, Jin X Zhang, Akul Singhania, Vivian Lee, Valeri H Terry, Douglas D Richman, Celsa A Spina, Christopher H Woelk

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in AIDS (London, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02475915 (A Randomized Study to Compare the Efficacy of Vorinostat/Hydroxychloroquine/Maraviroc), which is not on this map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.5field-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.

NCT02475915 phase1 / phase2completednot on this mapstarted 2015, after this paper: background citation

A Randomized Study to Compare the Efficacy of Vorinostat/Hydroxychloroquine/Maraviroc (VHM) in Controlling HIV After Treatment Interruption in Subjects Who Initiated ART During Acute HIV Infection

TypeinterventionalSponsorSEARCH Research FoundationRan2015 to 2016Enrolled15ConditionsAcute HIV InfectionArmsVorinostat, Hydroxychloroquine, Maraviroc, Tenofovir, Emtricitabine
3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 26 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

8 authors at 2 institutions in 2 countries.

Nadejda Beliakova-BethellDepartment of Medicine, University of California San Diego, La Jolla CA 92093-0679, USA. nbeliako@ucsd.edu
Jin X Zhang
Akul Singhania
Vivian Lee
Valeri H Terry
Douglas D Richman
Celsa A Spina
Christopher H Woelk
Apple (Israel) · ILUniversity of California, San Diego · US

Funding

VirologyP30AI036214 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SONIA JAIN · 1994 to 2026
$78.4M
Using NK Cells to eliminate the latent HIV reservoirU19AI096113 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LUCIW, PAUL · 2011 to 2015
$39.5M
HOPE Training GrantT32AI007384 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Sara Gianella Weibel, Scott L Letendre · 1990 to 2026
$9.7M
Targeting regulators of cellular gene transcription to impact HIV latencyP01AI080193 · NIAID · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · PI RICHMAN, DOUGLAS D · 2009 to 2010
$1.8M
Control of Latent/Persistent HIV Infection in Primary CD4 T CellsI01BX001160 · VA · VA SAN DIEGO HEALTHCARE SYSTEM · PI SPINA, CELSA A · 2011 to 2014
–
BLRD VA I01 BX001160NIAID NIH HHS 2T32AI007384-21A1NIAID NIH HHS AI007384NIAID NIH HHS AI080193NIAID NIH HHS AI096113NIAID NIH HHS AI36214NIAID NIH HHS P01 AI080193NIAID NIH HHS P30 AI036214NIAID NIH HHS T32 AI007384NIAID NIH HHS U19 AI096113
6 · The paper itself

Abstract

objectiveTo assess the off-target effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) in human primary CD4 T cells.

designA pharmacologically relevant concentration (340 nmol/l) of SAHA was shown to significantly increase histone hyperacetylation by 24 h and this length of treatment was selected to determine its impact on gene expression in primary CD4 T cells.

methodsIllumina Beadchips for microarray gene expression analysis were used to analyze differential gene expression between cells treated or not with SAHA with a paired analysis using multivariate permutation tests. Gene ontology, biological pathway and protein interaction network analyses were used to identify the higher order biological processes affected by SAHA treatment.

resultsModest modulation by SAHA was observed for 1847 genes with 80% confidence level of no more than 10% false positives. A thousand genes were upregulated by SAHA and 847 downregulated. Pathways and gene ontologies overrepresented in the list of differentially expressed genes included Glycolysis/Gluconeogenesis, tRNA Modification, and the Histone Acetyltransferase Complex. Protein interaction network analysis revealed that transcription factor c-Myc, which was downregulated by SAHA treatment at the mRNA level, interacts with a number of SAHA-responsive genes.

conclusionsThe effects on transcription by SAHA were sufficiently modest to support trials to activate HIV replication as part of an eradication strategy. SAHA did not appear to modulate proliferative or apoptotic processes to a great extent, which might impact the ability of patients to eradicate the virus reservoir following activation by HDACi treatment.

Indexed as

ApoptosisCD4-Positive T-LymphocytesCell ProliferationFemaleGene Expression Regulation, ViralHistone Deacetylase InhibitorsHIV-1HumansHydroxamic AcidsMaleReal-Time Polymerase Chain ReactionTranscriptomeVirus ReplicationVorinostatHistone Deacetylase InhibitorsHydroxamic AcidsVorinostat

Identifiers

PMID23221426
PMCPMC3752851
OpenAlexW2091524919

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.