Evidence map›Paper›PMID 18174227›Full record

ArticleNucleic acids research2008

Chromatinized templates reveal the requirement for the LEDGF/p75 PWWP domain during HIV-1 integration in vitro.

Yaïr Botbol, Nidhanapati K Raghavendra, Shaila Rahman, Alan Engelman, Marc Lavigne

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.7field-weighted citation impact, top 17% 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

35 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Cellular and molecular mechanisms of HIV-1 integration targeting.Cellular and molecular life sciences : CMLS · 2018
    Review
  9. Article
  10. Article
  11. Article
  12. Sites of retroviral DNA integration: From basic research to clinical applications.Critical reviews in biochemistry and molecular biology · 2016
    Review
  13. Review
  14. Review
  15. Molecular mechanisms of MLL-associated leukemia.International journal of hematology · 2015
    Review
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
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

5 authors at 3 institutions in 2 countries.

Yaïr BotbolDepartment of Virology, Unit of Structural Virology, Pasteur Institute, 25 rue du Dr Roux, 75724 Paris cedex 15, France.
Nidhanapati K Raghavendra
Shaila Rahman
Alan Engelman
Marc Lavigne
Harvard University · USDepartment of Virology · FRInstitut Pasteur · FR

Funding

Biochemical Mechanism of HIV DNA IntegrationR37AI039394 · NIAID · DANA-FARBER CANCER INST · PI Alan N. Engelman · 2010 to 2026
$10.2M
BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATIONR01AI039394 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 1996 to 2009
$3.8M
NIAID NIH HHS AI39394NIAID NIH HHS R01 AI039394NIAID NIH HHS R37 AI039394
6 · The paper itself

Abstract

Integration is an essential step in the retroviral lifecycle, and the lentiviral integrase binding protein lens epithelium-derived growth factor (LEDGF)/p75 plays a crucial role during human immunodeficiency virus type 1 (HIV-1) cDNA integration. In vitro, LEDGF/p75 stimulates HIV-1 integrase activity into naked target DNAs. Here, we demonstrate that this chromatin-associated protein also stimulates HIV-1 integration into reconstituted polynucleosome templates. Activation of integration depended on the LEDGF/p75-integrase interaction with either type of template. A differential requirement for the dominant DNA and chromatin-binding elements of LEDGF/p75 was however observed when using naked DNA versus polynucleosomes. With naked DNA, the complete removal of these N-terminal elements was required to abate cofactor function. With polynucleosomes, activation mainly depended on the PWWP domain, and to a lesser extent on nearby AT-hook DNA-binding motifs. GST pull-down assays furthermore revealed a role for the PWWP domain in binding to nucleosomes. These results are completely consistent with recent ex vivo studies that characterized the PWWP and integrase-binding domains of LEDGF/p75 as crucial for restoring HIV-1 infection to LEDGF-depleted cells. Our studies therefore establish novel in vitro conditions, highlighting chromatinized DNA as target acceptor templates, for physiologically relevant studies of LEDGF/p75 in lentiviral cDNA integration.

Indexed as

Virus IntegrationDNAHIV-1HIV IntegraseHumansIntercellular Signaling Peptides and ProteinsNucleosomesProtein Structure, TertiaryTemplates, GeneticDNAHIV IntegraseIntercellular Signaling Peptides and Proteinslens epithelium-derived growth factorNucleosomes

Identifiers

PMID18174227
PMCPMC2275106
OpenAlexW2148942598

What OpenQuestion holds

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LicenceCC BY-NC
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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.