Evidence map›Paper›PMID 19843699›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2009

Epigenetic activation of unintegrated HIV-1 genomes by gut-associated short chain fatty acids and its implications for HIV infection.

Boris Kantor, Hong Ma, Jennifer Webster-Cyriaque, Paul E Monahan, Tal Kafri

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
2.3field-weighted citation impact, top 11% 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

75 citing papers in PubMed, 97 citations in OpenAlex.

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  9. Engineering single-cycle MeV vector for CRISPR-Cas9 gene editing.Molecular therapy. Methods & clinical development · 2024
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15 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 3 institutions in 3 countries.

Boris KantorGene Therapy Center, University of North Carolina School of Medicine, Chapel Hill, NC 27514, USA.
Hong Ma
Jennifer Webster-Cyriaque
Paul E Monahan
Tal Kafri
Gene Therapy Laboratory · FRSegeberger Kliniken · DEUniversity of North Carolina at Chapel Hill · US

Funding

Resolving rate limiting steps for AAV vectorsP01HL066973 · NHLBI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI SAMULSKI, RICHARD J · 2001 to 2005
$9.3M
Nonintegrating Lentiviral Vectors Towards Clinical TrialsR01DK058702 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2001 to 2019
$5.0M
Novel Viral Vector Delivery for Efficient ShRNA ExpressionR21HL086406 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KAFRI, TAL · 2006 to 2007
$396k
NHLBI NIH HHS 5-PO1-HL066973-05NHLBI NIH HHS 5-R21-HL086406NHLBI NIH HHS P01 HL066973NHLBI NIH HHS R21 HL086406NIDDK NIH HHS 2-R01-DK058702-06NIDDK NIH HHS R01 DK058702
6 · The paper itself

Abstract

Integration of HIV-1 linear DNA into the host chromatin is an essential step in the viral life cycle. However, the majority of reverse-transcribed, nuclear-imported viral genomes remain episomal, either as linear or circular DNA. To date, these nonintegrated viral genomes are largely considered "dead-end products" of reverse transcription. Indeed, limited gene expression from nonintegrated HIV-1 has been reported, although the mechanism that renders nonintegrating HIV-1 genomes incapable of supporting efficient viral replication has not been fully elucidated. Here, we demonstrate that nonintegrating HIV-1 and HIV-1-based vector genomes are organized into chromatin structures and enriched with histone modifications typical of transcriptionally silenced chromatin. Gene expression and replication of nonintegrating HIV-1 was notably increased in vitro upon exposure to histone deacetylase inhibitors (HDACi) in the form of various short-chain fatty acids (SCFAs) known to be endogenously produced by normal microbial-gut flora. Furthermore, we demonstrated genetic and functional crosstalk between episomal and integrated vector/viral genomes, resulting in recombination between integrated and nonintegrated HIV-1, as well as mobilization of episomal vector genomes by productive viral particles encoded by integrated viral genomes. Finally, we propose a mechanism describing the role of episomal HIV-1 forms in the viral life cycle in a SCFA-rich gut environment.

Indexed as

ChromatinEpigenesis, GeneticFatty Acids, VolatileGastrointestinal TractGene SilencingGenetic VectorsGenome, ViralHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHIV-1HIV InfectionsHIV IntegraseHumansMacrophagesMonocytesChromatinFatty Acids, VolatileHistone Deacetylase InhibitorsHistone DeacetylasesHistonesHIV Integrase

Identifiers

PMID19843699
PMCPMC2773968
OpenAlexW2165834277

What OpenQuestion holds

Textmetadata
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.