Evidence map›Paper›PMID 29298886›Full record

ArticleJournal of virology2018

Class 1-Selective Histone Deacetylase (HDAC) Inhibitors Enhance HIV Latency Reversal while Preserving the Activity of HDAC Isoforms Necessary for Maximal HIV Gene Expression.

Thomas D Zaikos, Mark M Painter, Nadia T Sebastian Kettinger, Valeri H Terry, Kathleen L Collins

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

33 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Article
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  4. Article
  5. Review
  6. Latency Reversing Agents and the Road to an HIV CurePathogens (Basel, Switzerland) · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Hematopoietic Stem and Progenitor Cells (HSPCs).Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. 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

5 authors at 1 institution in 1 country.

Thomas D ZaikosDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Mark M PainterProgram in Immunology, University of Michigan, Ann Arbor, Michigan, USA.
Nadia T Sebastian KettingerProgram in Cellular and Molecular Biology, University of Michigan, Ann Arbor, Michigan, USA.
Valeri H TerryDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Kathleen L CollinsDepartment of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA klcollin@umich.edu.
University of Michigan–Ann Arbor · US

Funding

Michigan Institute for Clinical and Health Research (MICHR)UL1TR002240 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUMENG, JULIE C, MASHOUR, GEORGE ALEXANDER · 2017 to 2022
$54.9M
Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
RESEARCH TRAINING IN EXPERIMENTAL IMMUNOPATHOLOGYT32AI007413 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Bethany B. Moore · 1993 to 2026
$9.8M
NCATS NIH HHS UL1 TR000433
6 · The paper itself

Abstract

Combinations of drugs that affect distinct mechanisms of HIV latency aim to induce robust latency reversal leading to cytopathicity and elimination of the persistent HIV reservoir. Thus far, attempts have focused on combinations of protein kinase C (PKC) agonists and pan-histone deacetylase inhibitors (HDIs) despite the knowledge that HIV gene expression is regulated by class 1 histone deacetylases. We hypothesized that class 1-selective HDIs would promote more robust HIV latency reversal in combination with a PKC agonist than pan-HDIs because they preserve the activity of proviral factors regulated by non-class 1 histone deacetylases. Here, we show that class 1-selective agents used alone or with the PKC agonist bryostatin-1 induced more HIV protein expression per infected cell. In addition, the combination of entinostat and bryostatin-1 induced viral outgrowth, whereas bryostatin-1 combinations with pan-HDIs did not. When class 1-selective HDIs were used in combination with pan-HDIs, the amount of viral protein expression and virus outgrowth resembled that of pan-HDIs alone, suggesting that pan-HDIs inhibit robust gene expression induced by class 1-selective HDIs. Consistent with this, pan-HDI-containing combinations reduced the activity of NF-κB and Hsp90, two cellular factors necessary for potent HIV protein expression, but did not significantly reduce overall cell viability. An assessment of viral clearance from

Indexed as

BryostatinsCells, CulturedFemaleGene Expression Regulation, ViralHistone Deacetylase InhibitorsHistone DeacetylasesHIV-1HIV InfectionsHSP90 Heat-Shock ProteinsHumansMaleNF-kappa BProtein Kinase CVirus Latencybryostatin 1BryostatinsHistone Deacetylase InhibitorsHistone DeacetylasesHSP90 Heat-Shock ProteinsNF-kappa BProtein Kinase Chistone deacetylase inhibitorsHIVHsp90latency reversalshock and kill

Identifiers

PMID29298886
PMCPMC5827401
OpenAlexW2781927064

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.