Evidence map›Paper›PMID 19266025›Full record

ArticlePLoS pathogens2009

The SET complex acts as a barrier to autointegration of HIV-1.

Nan Yan, Peter Cherepanov, Janet E Daigle, Alan Engelman, Judy Lieberman

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 59 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 1 pooled it
3.4field-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

59 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.

  1. HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016
    Pooled it
  2. Article
  3. Article
  4. Article
  5. The Integrase: An Overview of a Key Player Enzyme in the Antiviral Scenario.International journal of molecular sciences · 2023
    Review
  6. Article
  7. Article
  8. Association ofFrontiers in genetics · 2022
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. ABCF1 Regulates dsDNA-induced Immune Responses in Human Airway Epithelial Cells.Frontiers in cellular and infection microbiology · 2020
    Article
  17. Review
  18. STING signaling and host defense against microbial infection.Experimental & molecular medicine · 2019
    Review
  19. Cellular and molecular mechanisms of HIV-1 integration targeting.Cellular and molecular life sciences : CMLS · 2018
    Review
  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.

Nan YanDepartment of Pediatrics, Immune Disease Institute, Harvard Medical School, Boston, Massachusetts, United States of America.
Peter Cherepanov
Janet E Daigle
Alan Engelman
Judy Lieberman
Dana-Farber Cancer Institute · USHarvard University Press · USImperial College London · GB

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
Nuclear Localization of HIV-1 Preintegration ComplexesR01AI052014 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 2003 to 2025
$11.4M
Biochemical Mechanism of HIV DNA IntegrationR37AI039394 · NIAID · DANA-FARBER CANCER INST · PI Alan N. Engelman · 2010 to 2026
$10.2M
Granzyme a Pathway of CTL-Mediated Cell DeathR01AI045587 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI LIEBERMAN, JUDY · 1999 to 2008
$4.4M
BIOCHEMICAL MECHANISM OF HIV DNA INTEGRATIONR01AI039394 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 1996 to 2009
$3.8M
Granzyme A Pathway of CTL-Mediated Cell DeathR56AI045587 · NIAID · IMMUNE DISEASE INSTITUTE, INC. · PI LIEBERMAN, JUDY · 2010 to 2010
$525k
Medical Research Council G0600009NIAID NIH HHS AI39394NIAID NIH HHS AI45587NIAID NIH HHS AI52014NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI039394NIAID NIH HHS R01 AI045587NIAID NIH HHS R01 AI052014NIAID NIH HHS R37 AI039394NIAID NIH HHS R56 AI045587
6 · The paper itself

Abstract

Retroviruses and retrotransposons are vulnerable to a suicidal pathway known as autointegration, which occurs when the 3'-ends of the reverse transcript are activated by integrase and then attack sites within the viral DNA. Retroelements have diverse strategies for suppressing autointegration, but how HIV-1 protects itself from autointegration is not well-understood. Here we show that knocking down any of the components of the SET complex, an endoplasmic reticulum-associated complex that contains 3 DNases (the base excision repair endonuclease APE1, 5'-3' exonuclease TREX1, and endonuclease NM23-H1), inhibits HIV-1 and HIV-2/SIV, but not MLV or ASV, infection. Inhibition occurs at a step in the viral life cycle after reverse transcription but before chromosomal integration. Antibodies to SET complex proteins capture HIV-1 DNA in the cytoplasm, suggesting a direct interaction between the SET complex and the HIV preintegration complex. Cloning of HIV integration sites in cells with knocked down SET complex components revealed an increase in autointegration, which was verified using a novel semi-quantitative nested PCR assay to detect autointegrants. When SET complex proteins are knocked down, autointegration increases 2-3-fold and chromosomal integration correspondingly decreases approximately 3-fold. Therefore, the SET complex facilitates HIV-1 infection by preventing suicidal autointegration.

Indexed as

Virus IntegrationAnimalsAvian Sarcoma VirusesBirdsDNA-(Apurinic or Apyrimidinic Site) LyaseDNA, ViralExodeoxyribonucleasesGene Knockdown TechniquesHIV-1HIV-2HIV InfectionsHumansJurkat CellsLeukemia Virus, MurineMiceNM23 Nucleoside Diphosphate KinasesAPEX1 protein, humanDNA-(Apurinic or Apyrimidinic Site) LyaseDNA, ViralExodeoxyribonucleasesNM23 Nucleoside Diphosphate KinasesNME1 protein, humanPhosphoproteinsRNA, Viralthree prime repair exonuclease 1

Identifiers

PMID19266025
PMCPMC2644782
OpenAlexW2031465961

What OpenQuestion holds

Textmetadata
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.