Evidence map›Paper›PMID 34872356›Full record

ArticlemBio2021

A Two-Color Haploid Genetic Screen Identifies Novel Host Factors Involved in HIV-1 Latency.

Michael Röling, Mahsa Mollapour Sisakht, Enrico Ne, Panagiotis Moulos, Raquel Crespo, Mateusz Stoszko, Elisa De Crignis, Helen Bodmer, Tsung Wai Kan, Maryam Akbarzadeh and 4 more

Open access · goldAbstract read
In one paragraph

Article in mBio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 27% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

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

14 authors at 2 institutions in 3 countries.

Michael RölingDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Mahsa Mollapour Sisakht *Department of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Enrico Ne *Department of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Panagiotis Moulos *Institute for Fundamental Biomedical Research, Biomedical Sciences Research Center Alexander Fleming, Vari, Greece.
Raquel Crespo *Department of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Mateusz StoszkoDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Elisa De CrignisDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Helen BodmerDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Tsung Wai KanDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Maryam AkbarzadehDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Vaggelis HarokoposInstitute for Fundamental Biomedical Research, Biomedical Sciences Research Center Alexander Fleming, Vari, Greece.
Pantelis HatzisInstitute for Fundamental Biomedical Research, Biomedical Sciences Research Center Alexander Fleming, Vari, Greece.
Robert-Jan PalstraDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.
Tokameh MahmoudiDepartment of Biochemistry, Erasmus University Medical Center, Rotterdam, the Netherlands.ORCID 0000-0002-2060-9353
Erasmus MC · NLAlexander Fleming Biomedical Sciences Research Center · GR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

To identify novel host factors as putative targets to reverse HIV-1 latency, we performed an insertional mutagenesis genetic screen in a latent HIV-1 infected pseudohaploid KBM7 cell line (Hap-Lat). Following mutagenesis, insertions were mapped to the genome, and bioinformatic analysis resulted in the identification of 69 candidate host genes involved in maintaining HIV-1 latency. A select set of candidate genes was functionally validated using short hairpin RNA (shRNA)-mediated depletion in latent HIV-1 infected J-Lat A2 and 11.1 T cell lines. We confirmed ADK, CHD9, CMSS1, EVI2B, EXOSC8, FAM19A, GRIK5, IRF2BP2, NF1, and USP15 as novel host factors involved in the maintenance of HIV-1 latency. Chromatin immunoprecipitation assays indicated that CHD9, a chromodomain helicase DNA-binding protein, maintains HIV-1 latency via direct association with the HIV-1 5' long terminal repeat (LTR), and its depletion results in increased histone acetylation at the HIV-1 promoter, concomitant with HIV-1 latency reversal. FDA-approved inhibitors 5-iodotubercidin, trametinib, and topiramate, targeting ADK, NF1, and GRIK5, respectively, were characterized for their latency reversal potential. While 5-iodotubercidin exhibited significant cytotoxicity in both J-Lat and primary CD4

Indexed as

HaploidyVirus LatencyCD4-Positive T-LymphocytesDNA-Binding ProteinsDNA HelicasesGene Expression Regulation, ViralHIV-1HIV InfectionsHost-Pathogen InteractionsHumansKainic Acid ReceptorsTrans-ActivatorsTranscription FactorsUbiquitin-Specific ProteasesVirus ActivationCHD9 protein, humanDNA-Binding ProteinsDNA HelicasesGRIK5 protein, humanIRF2BP2 protein, humanKainic Acid ReceptorsTrans-ActivatorsTranscription FactorsUbiquitin-Specific ProteasesUSP15 protein, humanhaploid forward genetic screenhost factorhuman immunodeficiency viruslatency

Identifiers

PMID34872356
PMCPMC8649776
OpenAlexW4200200743

What OpenQuestion holds

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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.