Evidence map›Paper›PMID 23042676›Full record

ArticleNucleic acids research2012

HRP2 determines the efficiency and specificity of HIV-1 integration in LEDGF/p75 knockout cells but does not contribute to the antiviral activity of a potent LEDGF/p75-binding site integrase inhibitor.

Hao Wang, Kellie A Jurado, Xiaolin Wu, Ming-Chieh Shun, Xiang Li, Andrea L Ferris, Steven J Smith, Pratiq A Patel, James R Fuchs, Peter Cherepanov and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

77 citing papers in PubMed, 100 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022
    Review
  19. Article
  20. Article

17 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

13 authors at 5 institutions in 2 countries.

Hao WangDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Kellie A Jurado
Xiaolin Wu
Ming-Chieh Shun
Xiang Li
Andrea L Ferris
Steven J Smith
Pratiq A Patel
James R Fuchs
Peter Cherepanov
Mamuka Kvaratskhelia
Stephen H Hughes
Alan Engelman
Harvard University Press · USFrederick National Laboratory for Cancer Research · USThe Ohio State University · USDana-Farber Cancer Institute · USScience Applications International Corporation (United States) · US

Funding

IntegraseZIABC011426 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HUGHES, STEPHEN H · 2012 to 2022
$14.0M
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
Novel Assay for HIV-1 Integrase InhibitorsR01AI081581 · NIAID · OHIO STATE UNIVERSITY · PI KVARATSKHELIA, MAMUKA · 2010 to 2012
$1.1M
Inhibitors Targeting HIV Integrase MultimersR21AI097044 · NIAID · OHIO STATE UNIVERSITY · PI KESSL, JACQUES J. · 2011 to 2012
$419k
Intramural NIH HHSMedical Research Council G1000917NIAID NIH HHS AI039394NIAID NIH HHS AI081581NIAID NIH HHS AI097044NIAID NIH HHS R37 AI039394
6 · The paper itself

Abstract

The binding of integrase (IN) to lens epithelium-derived growth factor (LEDGF)/p75 in large part determines the efficiency and specificity of HIV-1 integration. However, a significant residual preference for integration into active genes persists in Psip1 (the gene that encodes for LEDGF/p75) knockout (KO) cells. One other cellular protein, HRP2, harbors both the PWWP and IN-binding domains that are important for LEDGF/p75 co-factor function. To assess the role of HRP2 in HIV-1 integration, cells generated from Hdgfrp2 (the gene that encodes for HRP2) and Psip1/Hdgfrp2 KO mice were infected alongside matched control cells. HRP2 depleted cells supported normal infection, while disruption of Hdgfrp2 in Psip1 KO cells yielded additional defects in the efficiency and specificity of integration. These deficits were largely restored by ectopic expression of either LEDGF/p75 or HRP2. The double-KO cells nevertheless supported residual integration into genes, indicating that IN and/or other host factors contribute to integration specificity in the absence of LEDGF/p75 and HRP2. Psip1 KO significantly increased the potency of an allosteric inhibitor that binds the LEDGF/p75 binding site on IN, a result that was not significantly altered by Hdgfrp2 disruption. These findings help to rule out the host factor-IN interactions as the primary antiviral targets of LEDGF/p75-binding site IN inhibitors.

Indexed as

Virus IntegrationAcetatesAnimalsBinding SitesCell LineFibroblastsHIV-1HIV Integrase InhibitorsHumansIntercellular Signaling Peptides and ProteinsMiceMice, KnockoutQuinolinesAcetatesBI-D compoundhepatoma-derived growth factorHIV Integrase InhibitorsIntercellular Signaling Peptides and Proteinslens epithelium-derived growth factorQuinolines

Identifiers

PMID23042676
PMCPMC3526291
OpenAlexW2140346705

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.