Evidence map›Paper›PMID 25147212›Full record

ArticleNucleic acids research2014

Molecular mechanisms of retroviral integration site selection.

Mamuka Kvaratskhelia, Amit Sharma, Ross C Larue, Erik Serrao, Alan Engelman

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
6.8field-weighted citation impact, top 2% 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

86 citing papers in PubMed, 134 citations in OpenAlex.

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  11. Targeted gene delivery systems for T-cell engineering.Cellular oncology (Dordrecht, Netherlands) · 2024
    Review
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  15. Assessing avian leukosis virus proviral load and lesion correlates in fowl glioma-inducing virus-infected Japanese bantam chickens.Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc · 2023
    Article
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26 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

5 authors at 2 institutions in 1 country.

Mamuka KvaratskheliaCenter for Retrovirus Research and College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA alan_engelman@dfci.harvard.edu.
Amit SharmaCenter for Retrovirus Research and College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Ross C LarueCenter for Retrovirus Research and College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA.
Erik SerraoDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Alan EngelmanDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA alan_engelman@dfci.harvard.edu.
The Ohio State University · USHarvard University · US

Funding

Project 9P50GM103368 · NIGMS · SCRIPPS RESEARCH INSTITUTE, THE · PI SHARPLESS, KARL BARRY · 2012 to 2016
$20.0M
Nuclear Localization of HIV-1 Preintegration ComplexesR01AI052014 · NIAID · DANA-FARBER CANCER INSTITUTE · PI ENGELMAN, ALAN N. · 2003 to 2025
$11.4M
MOLECULAR BASIS OF VIRAL INFECTIVITYT32AI007245 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI Aaron Gregory Schmidt · 1985 to 2026
$11.3M
Structure and function of HIV-1 integraseR01AI062520 · NIAID · UNIVERSITY OF COLORADO DENVER · PI KVARATSKHELIA, MAMUKA · 2006 to 2020
$5.3M
Cellular Cofactors of Murine Leukemia Virus IntegraseR21AI109522 · NIAID · OHIO STATE UNIVERSITY · PI KVARATSKHELIA, MAMUKA · 2014 to 2015
$423k
NIAID NIH HHS AI052014NIAID NIH HHS AI062520NIAID NIH HHS R01 AI062520NIAID NIH HHS R21 AI109522NIAID NIH HHS T32 AI007245NIGMS NIH HHS GM103368NIGMS NIH HHS P50 GM103368
6 · The paper itself

Abstract

Retroviral replication proceeds through an obligate integrated DNA provirus, making retroviral vectors attractive vehicles for human gene-therapy. Though most of the host cell genome is available for integration, the process of integration site selection is not random. Retroviruses differ in their choice of chromatin-associated features and also prefer particular nucleotide sequences at the point of insertion. Lentiviruses including HIV-1 preferentially integrate within the bodies of active genes, whereas the prototypical gammaretrovirus Moloney murine leukemia virus (MoMLV) favors strong enhancers and active gene promoter regions. Integration is catalyzed by the viral integrase protein, and recent research has demonstrated that HIV-1 and MoMLV targeting preferences are in large part guided by integrase-interacting host factors (LEDGF/p75 for HIV-1 and BET proteins for MoMLV) that tether viral intasomes to chromatin. In each case, the selectivity of epigenetic marks on histones recognized by the protein tether helps to determine the integration distribution. In contrast, nucleotide preferences at integration sites seem to be governed by the ability for the integrase protein to locally bend the DNA duplex for pairwise insertion of the viral DNA ends. We discuss approaches to alter integration site selection that could potentially improve the safety of retroviral vectors in the clinic.

Indexed as

Virus IntegrationGenetic TherapyGenetic VectorsHIV-1HumansIntegrasesIntercellular Signaling Peptides and ProteinsMoloney murine leukemia virusIntegrasesIntercellular Signaling Peptides and Proteinslens epithelium-derived growth factor

Identifiers

PMID25147212
PMCPMC4176367
OpenAlexW2112702228

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.