Evidence map›Paper›PMID 19609362›Full record

ArticlePLoS pathogens2009

LEDGF/p75 proteins with alternative chromatin tethers are functional HIV-1 cofactors.

Anne M Meehan, Dyana T Saenz, James H Morrison, Jose A Garcia-Rivera, Mary Peretz, Manuel Llano, Eric M Poeschla

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

50 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Review
  10. Efficient Nuclease-Directed Integration of Lentivirus Vectors into the Human Ribosomal DNA Locus.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  11. Evidence for Tethering of Human Cytomegalovirus Genomes to Host Chromosomes.Frontiers in cellular and infection microbiology · 2020
    Article
  12. Article
  13. Review
  14. Cellular and molecular mechanisms of HIV-1 integration targeting.Cellular and molecular life sciences : CMLS · 2018
    Review
  15. Review
  16. Article
  17. Article
  18. The effects of cocaine on HIV transcription.Journal of neurovirology · 2016
    Review
  19. Article
  20. 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

7 authors at 2 institutions in 1 country.

Anne M MeehanDepartment of Molecular Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Dyana T Saenz
James H Morrison
Jose A Garcia-Rivera
Mary Peretz
Manuel Llano
Eric M Poeschla
Mayo Clinic · USThe University of Texas at El Paso · US

Funding

Women's Cancer ProgramP30CA015083 · NCI · MAYO CLINIC ROCHESTER · PI Felicity Enders · 1985 to 2026
$151.3M
TOXICOLOGY PROJECTG12RR008124 · NCRR · UNIVERSITY OF TEXAS EL PASO · PI WALSH, ELIZABETH J · 1992 to 2011
$20.8M
RISE Scholars Program at UTEPR25GM069621 · NIGMS · UNIVERSITY OF TEXAS EL PASO · PI AGUILERA, RENATO J · 2004 to 2021
$11.2M
LEDGF/p7 and HIV IntegrationR01AI077344 · NIAID · UNIVERSITY OF COLORADO DENVER · PI POESCHLA, ERIC M. · 2008 to 2018
$4.1M
NOVEL LENTIVIRAL VECTORS FOR SUSTAINED GENE EXPRESSIONR01AI047536 · NIAID · MAYO CLINIC ROCHESTER · PI POESCHLA, ERIC M. · 1999 to 2008
$1.8M
Molecular Mechanism of LEDGF/p75 in HIV IntegrationSC2GM082301 · NIGMS · UNIVERSITY OF TEXAS EL PASO · PI LLANO, MANUEL · 2008 to 2010
$407k
Lentiviral Genome ProcessingR21AI047536 · NIAID · MAYO CLINIC COLL OF MEDICINE, ROCHESTER · PI POESCHLA, ERIC M. · 2003 to 2003
$292k
NCI NIH HHS 5P30CA015083NCI NIH HHS P30 CA015083NCRR NIH HHS G12 RR008124NCRR NIH HHS G12RR008124NIAID NIH HHS AI47536NIAID NIH HHS AI77344NIAID NIH HHS R01 AI047536NIAID NIH HHS R01 AI077344NIAID NIH HHS R21 AI047536NIGMS NIH HHS R25 GM069621NIGMS NIH HHS R25GM069621NIGMS NIH HHS SC2 GM082301NIGMS NIH HHS SC2GM082301
6 · The paper itself

Abstract

LEDGF/p75 can tether over-expressed lentiviral integrase proteins to chromatin but how this underlies its integration cofactor role for these retroviruses is unclear. While a single integrase binding domain (IBD) binds integrase, a complex N-terminal domain ensemble (NDE) interacts with unknown chromatin ligands. Whether integration requires chromatin tethering per se, specific NDE-chromatin ligand interactions or other emergent properties of LEDGF/p75 has been elusive. Here we replaced the NDE with strongly divergent chromatin-binding modules. The chimeras rescued integrase tethering and HIV-1 integration in LEDGF/p75-deficient cells. Furthermore, chromatin ligands could reside inside or outside the nucleosome core, and could be protein or DNA. Remarkably, a short Kaposi's sarcoma virus peptide that binds the histone 2A/B dimer converted GFP-IBD from an integration blocker to an integration cofactor that rescues over two logs of infectivity. NDE mutants were corroborative. Chromatin tethering per se is a basic HIV-1 requirement and this rather than engagement of particular chromatin ligands is important for the LEDGF/p75 cofactor mechanism.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsAntigens, ViralAntiviral AgentsBase SequenceCell LineCells, CulturedChromatinDNA-Binding ProteinsGreen Fluorescent ProteinsHistonesHIV-1HIV InfectionsHIV IntegraseHumansMiceAdaptor Proteins, Signal TransducingAntigens, ViralAntiviral AgentsChromatinDNA-Binding ProteinsGreen Fluorescent ProteinsHistonesHIV Integraselatency-associated nuclear antigenNuclear ProteinsPeptide FragmentsProteasome Endopeptidase ComplexPSIP1 protein, humanRecombinant Fusion ProteinsTranscription Factors

Identifiers

PMID19609362
PMCPMC2706977
OpenAlexW1991352945

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.