Evidence map›Paper›PMID 33931637›Full record

ArticleNature communications2021

Selective cell death in HIV-1-infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir.

Shringar Rao, Cynthia Lungu, Raquel Crespo, Thijs H Steijaert, Alicja Gorska, Robert-Jan Palstra, Henrieke A B Prins, Wilfred van Ijcken, Yvonne M Mueller, Jeroen J A van Kampen and 6 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
9.6field-weighted citation impact, top 1% 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

37 citing papers in PubMed, 58 citations in OpenAlex.

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  11. Neonatal Fc receptor is a functional receptor for classical human astrovirus.Genes to cells : devoted to molecular & cellular mechanisms · 2024
    Article
  12. Overcoming fixation and permeabilization challenges in flow cytometry by optical barcoding and multi-pass acquisition.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2024
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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

16 authors at 1 institution in 1 country.

Shringar RaoDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Cynthia LunguDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
Raquel CrespoDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Thijs H SteijaertDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0001-8878-1494
Alicja GorskaDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.
Robert-Jan PalstraDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-4600-2303
Henrieke A B PrinsDepartment of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1452-7271
Wilfred van IjckenErasmus Centre for Biomics, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-0421-8301
Yvonne M MuellerDepartment of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-4654-7509
Jeroen J A van KampenDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
Annelies VerbonDepartment of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.
Peter D KatsikisDepartment of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0001-7690-5218
Charles A B BoucherDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.
Casper RokxDepartment of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-1904-6450
Rob A GrutersDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-8486-5903
Tokameh MahmoudiDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, The Netherlands. t.mahmoudi@erasmusmc.nl.ORCID http://orcid.org/0000-0002-2060-9353
Erasmus MC · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

An innovative approach to eliminate HIV-1-infected cells emerging out of latency, the major hurdle to HIV-1 cure, is to pharmacologically reactivate viral expression and concomitantly trigger intracellular pro-apoptotic pathways in order to selectively induce cell death (ICD) of infected cells, without reliance on the extracellular immune system. In this work, we demonstrate the effect of DDX3 inhibitors on selectively inducing cell death in latent HIV-1-infected cell lines, primary CD4+ T cells and in CD4+ T cells from cART-suppressed people living with HIV-1 (PLWHIV). We used single-cell FISH-Flow technology to characterise the contribution of viral RNA to inducing cell death. The pharmacological targeting of DDX3 induced HIV-1 RNA expression, resulting in phosphorylation of IRF3 and upregulation of IFNβ. DDX3 inhibition also resulted in the downregulation of BIRC5, critical to cell survival during HIV-1 infection, and selectively induced apoptosis in viral RNA-expressing CD4+ T cells but not bystander cells. DDX3 inhibitor treatment of CD4+ T cells from PLWHIV resulted in an approximately 50% reduction of the inducible latent HIV-1 reservoir by quantitation of HIV-1 RNA, by FISH-Flow, RT-qPCR and TILDA. This study provides proof of concept for pharmacological reversal of latency coupled to induction of apoptosis towards the elimination of the inducible reservoir.

Indexed as

Anti-Retroviral AgentsApoptosisAzepinesCD4-Positive T-LymphocytesCell DeathCell SurvivalDEAD-box RNA HelicasesEnzyme InhibitorsHIV-1HIV InfectionsHumansImidazolesIn Situ Hybridization, FluorescenceInterferon-betaInterferon Regulatory Factor-3Jurkat Cells3,7-dihydro-3,7-bis((4-methoxyphenyl)methyl)-2H-diimidazo(4,5-d:4',5'-f)(1,3)diazepin-2-oneAnti-Retroviral AgentsAzepinesBIRC5 protein, humanDDX3X protein, humanDEAD-box RNA HelicasesEnzyme InhibitorsImidazolesInterferon-betaInterferon Regulatory Factor-3IRF3 protein, humanRNA, ViralSurvivin

Identifiers

PMID33931637
PMCPMC8087668
OpenAlexW3158214190

What OpenQuestion holds

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Registered trials

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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.