Evidence map›Paper›PMID 25808736›Full record

ArticleRetrovirology2015

Integrase inhibitor reversal dynamics indicate unintegrated HIV-1 dna initiate de novo integration.

Sylvain Thierry, Soundasse Munir, Eloïse Thierry, Frédéric Subra, Hervé Leh, Alessia Zamborlini, Dyana Saenz, David N Levy, Paul Lesbats, Ali Saïb and 4 more

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.3field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 39 citations in OpenAlex.

  1. Trial
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  9. 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
  10. Article
  11. Immune Control of HIV.Journal of life sciences (Westlake Village, Calif.) · 2019
    Article
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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

14 authors at 4 institutions in 2 countries.

Sylvain Thierry
Soundasse Munir
Eloïse Thierry
Frédéric Subra
Hervé Leh
Alessia Zamborlini
Dyana Saenz
David N Levy
Paul Lesbats
Ali Saïb
Vincent Parissi
Eric Poeschla
Eric Deprez
Olivier Delelis
École Normale Supérieure Paris-Saclay · FRCentre National de la Recherche Scientifique · FRUniversity of Colorado Denver · USNew York University · US

Funding

LEDGF/p7 and HIV IntegrationR01AI077344 · NIAID · UNIVERSITY OF COLORADO DENVER · PI POESCHLA, ERIC M. · 2008 to 2018
$4.1M
HIV-1 Replication Without IntegrationR01AI078783 · NIAID · NEW YORK UNIVERSITY · PI LEVY, DAVID N · 2009 to 2013
$2.1M
Viruis Dynamics and Multiple Infection of Cells: Computational and Experimental AR01AI093998 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI LEVY, DAVID N, WODARZ, DOMINIK F · 2011 to 2014
$1.5M
NIAID NIH HHS R01 AI077344NIAID NIH HHS R01 AI078783
6 · The paper itself

Abstract

backgroundGenomic integration, an obligate step in the HIV-1 replication cycle, is blocked by the integrase inhibitor raltegravir. A consequence is an excess of unintegrated viral DNA genomes, which undergo intramolecular ligation and accumulate as 2-LTR circles. These circularized genomes are also reliably observed in vivo in the absence of antiviral therapy and they persist in non-dividing cells. However, they have long been considered as dead-end products that are not precursors to integration and further viral propagation.

resultsHere, we show that raltegravir action is reversible and that unintegrated viral DNA is integrated in the host cell genome after raltegravir removal leading to HIV-1 replication. Using quantitative PCR approach, we analyzed the consequences of reversing prolonged raltegravir-induced integration blocks. We observed, after RAL removal, a decrease of 2-LTR circles and a transient increase of linear DNA that is subsequently integrated in the host cell genome and fuel new cycles of viral replication.

conclusionsOur data highly suggest that 2-LTR circles can be used as a reserve supply of genomes for proviral integration highlighting their potential role in the overall HIV-1 replication cycle.

Indexed as

Virus IntegrationVirus ReplicationCell LineDNA, ViralHIV-1HIV IntegraseHIV Integrase InhibitorsHumansReal-Time Polymerase Chain ReactionDNA, ViralHIV IntegraseHIV Integrase Inhibitorsp31 integrase protein, Human immunodeficiency virus 1

Identifiers

PMID25808736
PMCPMC4372172
OpenAlexW2117001989

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.