Evidence map›Paper›PMID 22145813›Full record

ArticleRetrovirology2011

Inhibition of HIV-1 infection by TNPO3 depletion is determined by capsid and detectable after viral cDNA enters the nucleus.

Alberto De Iaco, Jeremy Luban

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% 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

73 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 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
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  4. Complex Relationships between HIV-1 Integrase and Its Cellular Partners.International journal of molecular sciences · 2022
    Review
  5. Transportin-3 Facilitates Uncoating of Influenza A Virus.International journal of molecular sciences · 2022
    Article
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  7. Review
  8. Inhibition of autophagy rescues muscle atrophy in a LGMDD2 Drosophila model.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021
    Article
  9. Review
  10. Article
  11. Review
  12. Measuring the subcellular compartmentalization of viral infections by protein complementation assay.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

13 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

2 authors at 1 institution in 1 country.

Alberto De IacoDepartment of Microbiology and Molecular Medicine, University of Geneva, 1 Rue Michel Servet, CH-1211 Geneva, Switzerland.
Jeremy Luban
University of Geneva · CH

Funding

Cyclophilin A Function in the Immune SystemR01AI059159 · NIAID · UNIVERSITY OF GENEVA · PI LUBAN, JEREMY · 2006 to 2011
$1.4M
NIAID NIH HHS R01AI59159
6 · The paper itself

Abstract

backgroundHIV-1 infects non-dividing cells. This implies that the virus traverses the nuclear pore before it integrates into chromosomal DNA. Recent studies demonstrated that TNPO3 is required for full infectivity of HIV-1. The fact that TNPO3 is a karyopherin suggests that it acts by directly promoting nuclear entry of HIV-1. Some studies support this hypothesis, while others have failed to do so. Additionally, some studies suggest that TNPO3 acts via HIV-1 Integrase (IN), and others indicate that it acts via capsid (CA).

resultsTo shed light on the mechanism by which TNPO3 contributes to HIV-1 infection we engineered a panel of twenty-seven single-cycle HIV-1 vectors each bearing a different CA mutation and characterized them for the ability to transduce cells in which TNPO3 had been knocked down (KD). Fourteen CA mutants were relatively TNPO3-independent, as compared to wild-type (WT) HIV-1. Two mutants were more TNPO3-dependent than the WT, and eleven mutants were actually inhibited by TNPO3. The efficiency of the synthesis of viral cDNA, 2-LTR circles, and proviral DNA was then assessed for WT HIV-1 and three select CA mutants. Controls included rescue of TNPO3 KD with non-targetable coding sequence, RT- and IN- mutant viruses, and pharmacologic inhibitors of RT and IN. TNPO3 KD blocked transduction and establishment of proviral DNA by wild-type HIV-1 with no significant effect on the level of 2-LTR circles. PCR results were confirmed by achieving TNPO3 KD using two different methodologies (lentiviral vector and siRNA oligonucleotide transfection); by challenging three different cell types; by using two different challenge viruses, each necessitating different sets of PCR primers; and by pseudotyping virus with VSV G or using HIV-1 Env.

conclusionTNPO3 promotes HIV-1 infectivity at a step in the virus life cycle that is detectable after the preintegration complex arrives in the nucleus and CA is the viral determinant for TNPO3 dependence.

Indexed as

beta KaryopherinsCapsidCapsid ProteinsCell Line, TumorCell NucleusDNA, ViralGene Knockdown TechniquesHeLa CellsHIV-1HIV InfectionsHIV IntegraseHIV Long Terminal RepeatHumansMicroRNAsMutationNuclear Envelopebeta KaryopherinsCapsid ProteinsDNA, ViralHIV IntegraseMicroRNAsp31 integrase protein, Human immunodeficiency virus 1Reverse Transcriptase InhibitorsRNA, Small InterferingTNPO3 protein, human

Identifiers

PMID22145813
PMCPMC3267670
OpenAlexW2112500845

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.