Evidence map›Paper›PMID 32210344›Full record

ArticleScientific reports2020

CRISPR-based gene knockout screens reveal deubiquitinases involved in HIV-1 latency in two Jurkat cell models.

Anurag Rathore, Sho Iketani, Pengfei Wang, Manxue Jia, Vincent Sahi, David D Ho

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.5field-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

32 citing papers in PubMed, 51 citations in OpenAlex.

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  12. TDP-43 Epigenetic Facets and Their Neurodegenerative Implications.International journal of molecular sciences · 2023
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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

6 authors at 3 institutions in 1 country.

Anurag RathoreAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Sho IketaniAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Pengfei WangAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Manxue JiaAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, 10032, USA.
Vincent SahiAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, 10032, USA.
David D HoAaron Diamond AIDS Research Center, Columbia University Irving Medical Center, New York, NY, 10032, USA. dh2994@cumc.columbia.edu.
Columbia University · USAaron Diamond AIDS Research Center · USColumbia University Irving Medical Center · US

Funding

Bispecific-Antibody-Drug Conjugates for Selective Targeting and Activation of the HIV Latent ReservoirR01AI134328 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HO, DAVID D · 2017 to 2021
$2.7M
Columbia University Graduate Training Program in Microbiology and ImmunologyT32AI106711 · NIAID · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Nicholas Arpaia, Uttiya Basu · 2014 to 2026
$2.1M
NIAID NIH HHS R01 AI134328NIAID NIH HHS T32 AI106711
6 · The paper itself

Abstract

The major barrier to a HIV-1 cure is the persistence of latent genomes despite treatment with antiretrovirals. To investigate host factors which promote HIV-1 latency, we conducted a genome-wide functional knockout screen using CRISPR-Cas9 in a HIV-1 latency cell line model. This screen identified IWS1, POLE3, POLR1B, PSMD1, and TGM2 as potential regulators of HIV-1 latency, of which PSMD1 and TMG2 could be confirmed pharmacologically. Further investigation of PSMD1 revealed that an interacting enzyme, the deubiquitinase UCH37, was also involved in HIV-1 latency. We therefore conducted a comprehensive evaluation of the deubiquitinase family by gene knockout, identifying several deubiquitinases, UCH37, USP14, OTULIN, and USP5 as possible HIV-1 latency regulators. A specific inhibitor of USP14, IU1, reversed HIV-1 latency and displayed synergistic effects with other latency reversal agents. IU1 caused degradation of TDP-43, a negative regulator of HIV-1 transcription. Collectively, this study is the first comprehensive evaluation of deubiquitinases in HIV-1 latency and establishes that they may hold a critical role.

Indexed as

CRISPR-Cas SystemsVirus LatencyDeubiquitinating Enzyme CYLDDeubiquitinating EnzymesDNA-Binding ProteinsDNA-Directed RNA PolymerasesDNA Polymerase IIIEndopeptidasesEnzyme InhibitorsGene Knockout TechniquesHIV-1Host-Pathogen InteractionsHumansJurkat CellsNucleoproteinsProteasome Endopeptidase ComplexCYLD protein, humanDeubiquitinating Enzyme CYLDDeubiquitinating EnzymesDNA-Binding ProteinsDNA-Directed RNA PolymerasesDNA Polymerase IIIEndopeptidasesEnzyme InhibitorsIws1 protein, humanNucleoproteinsPOLE3 protein, humanProteasome Endopeptidase ComplexPSMD1 protein, humanRNA-Binding ProteinsTARDBP protein, humanTranscription Factorsubiquitin isopeptidaseUbiquitin ThiolesteraseUCHL5 protein, humanUSP14 protein, human

Identifiers

PMID32210344
PMCPMC7093534
OpenAlexW3013091596

What OpenQuestion holds

Textmetadata
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.