Evidence map›Paper›PMID 29170390›Full record

ArticleScientific reports2017

Systems analysis of latent HIV reversal reveals altered stress kinase signaling and increased cell death in infected T cells.

Linda E Fong, Endah S Sulistijo, Kathryn Miller-Jensen

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

8 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. HibeRNAtion: HIV-1 RNA Metabolism and Viral Latency.Frontiers in cellular and infection microbiology · 2022
    Review
  5. Article
  6. Article
  7. Review
  8. Review
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

3 authors at 1 institution in 1 country.

Linda E FongDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Endah S SulistijoDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Kathryn Miller-JensenDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA. kathryn.miller-jensen@yale.edu.
Yale University · US

Funding

Discovery and characterization of modified signaling networks in latent HIV-infected T cells using CyTOFR21AI132013 · NIAID · YALE UNIVERSITY · PI MILLER-JENSEN, KATHRYN · 2017 to 2018
$432k
NIAID NIH HHS R21 AI132013
6 · The paper itself

Abstract

Viral latency remains the most significant obstacle to HIV eradication. Clinical strategies aim to purge the latent CD4+ T cell reservoir by activating viral expression to induce death, but are undercut by the inability to target latently infected cells. Here we explored the acute signaling response of latent HIV-infected CD4+ T cells to identify dynamic phosphorylation signatures that could be targeted for therapy. Stimulation with CD3/CD28, PMA/ionomycin, or latency reversing agents prostratin and SAHA, yielded increased phosphorylation of IκBα, ERK, p38, and JNK in HIV-infected cells across two in vitro latency models. Both latent infection and viral protein expression contributed to changes in perturbation-induced signaling. Data-driven statistical models calculated from the phosphorylation signatures successfully classified infected and uninfected cells and further identified signals that were functionally important for regulating cell death. Specifically, the stress kinase pathways p38 and JNK were modified in latently infected cells, and activation of p38 and JNK signaling by anisomycin resulted in increased cell death independent of HIV reactivation. Our findings suggest that altered phosphorylation signatures in infected T cells provide a novel strategy to more selectively target the latent reservoir to enhance eradication efforts.

Indexed as

CD4-Positive T-LymphocytesCell DeathHIV-1HIV InfectionsHumansPhosphorylationT-LymphocytesVirus ActivationVirus Latency

Identifiers

PMID29170390
PMCPMC5701066
OpenAlexW2769683704

What OpenQuestion holds

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LicenceCC BY
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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.