Evidence map›Paper›PMID 21987578›Full record

ArticleThe Journal of biological chemistry2011

Role of the PWWP domain of lens epithelium-derived growth factor (LEDGF)/p75 cofactor in lentiviral integration targeting.

Rik Gijsbers, Sofie Vets, Jan De Rijck, Karen E Ocwieja, Keshet Ronen, Nirav Malani, Frederic D Bushman, Zeger Debyser

RetractedOpen access · hybridAbstract readRetracted Publication
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.5field-weighted citation impact, top 12% 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

27 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Interactions between Retroviruses and the Host Cell Genome.Molecular therapy. Methods & clinical development · 2018
    Review
  5. Nuclear landscape of HIV-1 infection and integration.Nature reviews. Microbiology · 2017
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Interrogating HIV integrase for compounds that bind--a SAMPL challenge.Journal of computer-aided molecular design · 2014
    Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

Rik GijsbersDivision of Molecular Medicine, KU Leuven, 3000 Leuven, Belgium. Electronic address: rik.gijsbers@med.kuleuven.be.
Sofie VetsDivision of Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
Jan De RijckDivision of Molecular Medicine, KU Leuven, 3000 Leuven, Belgium.
Karen E OcwiejaDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
Keshet RonenDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
Nirav MalaniDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
Frederic D BushmanDepartment of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104.
Zeger DebyserDivision of Molecular Medicine, KU Leuven, 3000 Leuven, Belgium. Electronic address: zeger.debyser@med.kuleuven.be.
KU Leuven · BEUniversity of Pennsylvania · US

Funding

Lentivirus-based Immunogene Therapy for HIV InfectionU19AI066290 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2005 to 2009
$7.2M
TRAINING IN VIROLOGYT32AI007324 · NIAID · WISTAR INSTITUTE · PI Paul Bates, Matthew D. Weitzman · 1989 to 2026
$6.8M
Favored Sites for HIV Integration in the Human GenomeR01AI052845 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D · 2002 to 2017
$5.6M
NIAID NIH HHS AI52845NIAID NIH HHS AI66290NIAID NIH HHS R01 AI052845NIAID NIH HHS T32 AI007324NIAID NIH HHS T32 AI-07324-17NIAID NIH HHS U19 AI066290
6 · The paper itself

Abstract

LEDGF/p75 is a chromatin-interacting, cellular cofactor of HIV integrase that dictates lentiviral integration site preference. In this study we determined the role of the PWWP domain of LEDGF/p75 in tethering and targeting of the lentiviral pre-integration complex, employing potent knockdown cell lines allowing analysis in the absence of endogenous LEDGF/p75. Deletion of the PWWP domain resulted in a diffuse subnuclear distribution pattern, loss of interaction with condensed chromatin, and failure to rescue proviral integration, integration site distribution, and productive virus replication. Substitution of the PWWP domain of LEDGF/p75 with that of hepatoma-derived growth factor or HDGF-related protein-2 rescued viral replication and lentiviral integration site distribution in LEDGF/p75-depleted cells. Replacing all chromatin binding elements of LEDGF/p75 with full-length hepatoma-derived growth factor resulted in more integration in genes combined with a preference for CpG islands. In addition, we showed that any PWWP domain targets SMYD1-like sequences. Analysis of integration preferences of lentiviral vectors for epigenetic marks indicates that the PWWP domain is critical for interactions specifying the relationship of integration sites to regions enriched in specific histone post-translational modifications.

Indexed as

Adaptor Proteins, Signal TransducingAmino Acid SequenceChromatinCpG IslandsDNA-Binding ProteinsHeLa CellsHIV-1HumansMuscle ProteinsProtein Structure, TertiarySequence DeletionTranscription FactorsVirus IntegrationAdaptor Proteins, Signal TransducingChromatinDNA-Binding ProteinsMuscle ProteinsPSIP1 protein, humanSMYD1 protein, humanTranscription Factors

Identifiers

PMID21987578
PMCPMC3308889
OpenAlexW2012589152

What OpenQuestion holds

Textmetadata
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.