Evidence map›Paper›PMID 26545813›Full record

ArticleGenes & development2015

LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes.

Parmit Kumar Singh, Matthew R Plumb, Andrea L Ferris, James R Iben, Xiaolin Wu, Hind J Fadel, Brian T Luke, Caroline Esnault, Eric M Poeschla, Stephen H Hughes and 2 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
–field-weighted citation impact
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

75 citing papers in PubMed, 113 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Structural rearrangements in the nucleus localize latent HIV proviruses to a perinucleolar compartment supportive of reactivation.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Capsid-host interactions for HIV-1 ingress.Microbiology and molecular biology reviews : MMBR · 2023
    Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

15 more citing papers are in PubMed but not listed here.

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

12 authors at 7 institutions in 1 country.

Parmit Kumar SinghSection on Eukaryotic Transposable Elements, Program in Cellular Regulation and Metabolism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA;
Matthew R PlumbCenter for Retrovirus Research, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA;
Andrea L FerrisHIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702, USA;
James R IbenProgram in Genomics of Differentiation, Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA;
Xiaolin WuLeidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA;
Hind J FadelDepartment of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA;
Brian T LukeAdvanced Biomedical Computing Center, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, Maryland, 21702, USA;
Caroline EsnaultSection on Eukaryotic Transposable Elements, Program in Cellular Regulation and Metabolism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA;
Eric M PoeschlaDivision of Infectious Diseases, University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
Stephen H HughesHIV Drug Resistance Program, National Cancer Institute, Frederick, Maryland 21702, USA;
Mamuka KvaratskheliaCenter for Retrovirus Research, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA;
Henry L LevinSection on Eukaryotic Transposable Elements, Program in Cellular Regulation and Metabolism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA;
Eunice Kennedy Shriver National Institute of Child Health and Human Development · USFrederick National Laboratory for Cancer Research · USThe Ohio State University · USMayo Clinic · USNational Cancer Institute · USNational Institutes of Health · USUniversity of Colorado Denver · US

Funding

Regulation And Function Of RetroelementsZIAHD001009 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI LEVIN, HENRY L. · 2009 to 2025
$21.8M
Molecular Genomics Sequencing Core FacilityZICHD008958 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI MAHADEVAN, VIVEK · 2016 to 2025
$19.0M
IntegraseZIABC011426 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HUGHES, STEPHEN H · 2012 to 2022
$14.0M
Structure and function of HIV-1 integraseR01AI062520 · NIAID · UNIVERSITY OF COLORADO DENVER · PI KVARATSKHELIA, MAMUKA · 2006 to 2020
$5.3M
LEDGF/p7 and HIV IntegrationR01AI077344 · NIAID · UNIVERSITY OF COLORADO DENVER · PI POESCHLA, ERIC M. · 2008 to 2018
$4.1M
CCR NIH HHS HHSN261200800001CIntramural NIH HHSNCI NIH HHS HHSN261200800001ENIAID NIH HHS AI062520NIAID NIH HHS AI77344NIAID NIH HHS R01 AI062520NIAID NIH HHS R01 AI077344
6 · The paper itself

Abstract

The host chromatin-binding factor LEDGF/p75 interacts with HIV-1 integrase and directs integration to active transcription units. To understand how LEDGF/p75 recognizes transcription units, we sequenced 1 million HIV-1 integration sites isolated from cultured HEK293T cells. Analysis of integration sites showed that cancer genes were preferentially targeted, raising concerns about using lentivirus vectors for gene therapy. Additional analysis led to the discovery that introns and alternative splicing contributed significantly to integration site selection. These correlations were independent of transcription levels, size of transcription units, and length of the introns. Multivariate analysis with five parameters previously found to predict integration sites showed that intron density is the strongest predictor of integration density in transcription units. Analysis of previously published HIV-1 integration site data showed that integration density in transcription units in mouse embryonic fibroblasts also correlated strongly with intron number, and this correlation was absent in cells lacking LEDGF. Affinity purification showed that LEDGF/p75 is associated with a number of splicing factors, and RNA sequencing (RNA-seq) analysis of HEK293T cells lacking LEDGF/p75 or the LEDGF/p75 integrase-binding domain (IBD) showed that LEDGF/p75 contributes to splicing patterns in half of the transcription units that have alternative isoforms. Thus, LEDGF/p75 interacts with splicing factors, contributes to exon choice, and directs HIV-1 integration to transcription units that are highly spliced.

Indexed as

HEK293 CellsHIV-1HumansIntercellular Signaling Peptides and ProteinsIntronsProtein BindingProtein Structure, TertiaryRNA SplicingVirus IntegrationIntercellular Signaling Peptides and Proteinslens epithelium-derived growth factorHIV-1integrationLEDGFmRNA splicingp75retrovirus

Identifiers

PMID26545813
PMCPMC4647561
OpenAlexW2166267844

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.