Evidence map›Paper›PMID 36094316›Full record

ArticleJournal of virology2022

HIV-1 Preintegration Complex Preferentially Integrates the Viral DNA into Nucleosomes Containing Trimethylated Histone 3-Lysine 36 Modification and Flanking Linker DNA.

Nicklas Sapp, Nathaniel Burge, Khan Cox, Prem Prakash, Muthukumar Balasubramaniam, Santosh Thapa, Devin Christensen, Min Li, Jared Linderberger, Mamuka Kvaratskhelia and 4 more

Abstract read
In one paragraph

Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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.

Nicklas SappThe Center for AIDS Health Disparities Research, Meharry Medical Collegegrid.259870.1, Nashville, Tennessee, USA.
Nathaniel BurgeDepartment of Chemistry and Biochemistry, Ohio State University, Columbus, Ohio, USA.
Khan CoxDepartment of Chemistry and Biochemistry, Ohio State University, Columbus, Ohio, USA.
Prem PrakashThe Center for AIDS Health Disparities Research, Meharry Medical Collegegrid.259870.1, Nashville, Tennessee, USA.
Muthukumar BalasubramaniamThe Center for AIDS Health Disparities Research, Meharry Medical Collegegrid.259870.1, Nashville, Tennessee, USA.
Santosh ThapaThe Center for AIDS Health Disparities Research, Meharry Medical Collegegrid.259870.1, Nashville, Tennessee, USA.
Devin ChristensenDepartment of Biochemistry, University of Utah, Salt Lake City, Utah, USA.
Min LiLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Jared LinderbergerDivision of Infectious Diseases, University of Colorado, Aurora, Colorado, USA.
Mamuka KvaratskheliaDivision of Infectious Diseases, University of Colorado, Aurora, Colorado, USA.ORCID 0000-0003-3800-0033
Jui PandhareThe Center for AIDS Health Disparities Research, Meharry Medical Collegegrid.259870.1, Nashville, Tennessee, USA.
Robert CraigieLaboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Michael G PoirierDepartment of Microbiology, Immunology, and Physiology, Meharry Medical Collegegrid.259870.1, Nashville, Tennessee, USA.
Chandravanu DashThe Center for AIDS Health Disparities Research, Meharry Medical Collegegrid.259870.1, Nashville, Tennessee, USA.ORCID 0000-0003-4466-8355

Funding

The RCMI Program in Health Disparities Research at Meharry Medical College - SupplementU54MD007586 · NIMHD · MEHARRY MEDICAL COLLEGE · PI Maureen Sanderson · 2017 to 2026
$48.2M
Tennessee CFAR: Implementation of Culturally Responsive Trauma-Informed Care with Youth with HIV in Memphis, TNP30AI110527 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Carolyn Audet · 2015 to 2026
$27.5M
Technologies and Resources CoreU54MD007593 · NIMHD · MEHARRY MEDICAL COLLEGE · PI ADUNYAH, SAMUEL EVANS · 2012 to 2018
$24.7M
THE MEHARRY RISE INITIATIVER25GM059994 · NIGMS · MEHARRY MEDICAL COLLEGE · PI MOTLEY-JOHNSON, EVANGELINE D · 1999 to 2021
$23.0M
Meharry RCMI Program in Women's Health ResearchG12MD007586 · NIMHD · MEHARRY MEDICAL COLLEGE · PI HILDRETH, JAMES E · 2012 to 2016
$7.8M
Role of GRIN2 in ART and SUD associated neurological deficits.R01DA057204 · NIDA · MEHARRY MEDICAL COLLEGE · PI Chandravanu Dash · 2022 to 2026
$3.7M
Defining the nuclear import pathways of HIV-1R01AI162694 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI CAMPBELL, EDWARD M · 2021 to 2024
$2.9M
Spatiotemporal Staging of the HIV-1 Preintegration complexR01AI170228 · NIAID · MEHARRY MEDICAL COLLEGE · PI Chandravanu Dash · 2022 to 2026
$2.8M
The effect of HIV and cocaine abuse on semen exosome composition and functionR01DA042348 · NIDA · UNIVERSITY OF IOWA · PI OKEOMA, CHIOMA M · 2016 to 2020
$2.7M
Multimeric HIV-1 Integrase InhibitorsR01AI143649 · NIAID · UNIVERSITY OF COLORADO DENVER · PI KVARATSKHELIA, MAMUKA · 2019 to 2023
$2.5M
Methamphetamine Research Program at Meharry Medical CollegeR24DA036420 · NIDA · MEHARRY MEDICAL COLLEGE · PI CHARLTON, CLIVEL G. · 2014 to 2018
$2.3M
Role of the Viral Capsid in HIV-1 IntegrationR01AI136740 · NIAID · MEHARRY MEDICAL COLLEGE · PI Chandravanu Dash · 2019 to 2026
$2.2M
NIAID NIH HHS F31 AI150488NIAID NIH HHS P30 AI110527NIAID NIH HHS R01 AI136740NIAID NIH HHS R01 AI143649NIAID NIH HHS R01 AI162694NIAID NIH HHS R01 AI170228NIAID NIH HHS R25 AI164610NIAID NIH HHS R56 AI122960NIDA NIH HHS R01 DA042348NIDA NIH HHS R01 DA057204NIDA NIH HHS R24 DA036420NIGMS NIH HHS R25 GM059994NIMHD NIH HHS G12 MD007586NIMHD NIH HHS U54 MD007586NIMHD NIH HHS U54 MD007593
6 · The paper itself

Abstract

HIV-1 DNA is preferentially integrated into chromosomal hot spots by the preintegration complex (PIC). To understand the mechanism, we measured the DNA integration activity of PICs-extracted from infected cells-and intasomes, biochemically assembled PIC substructures using a number of relevant target substrates. We observed that PIC-mediated integration into human chromatin is preferred compared to genomic DNA. Surprisingly, nucleosomes lacking histone modifications were not preferred integration compared to the analogous naked DNA. Nucleosomes containing the trimethylated histone 3 lysine 36 (H3K36me3), an epigenetic mark linked to active transcription, significantly stimulated integration, but the levels remained lower than the naked DNA. Notably, H3K36me3-modified nucleosomes with linker DNA optimally supported integration mediated by the PIC but not by the intasome. Interestingly, optimal intasome-mediated integration required the cellular cofactor LEDGF. Unexpectedly, LEDGF minimally affected PIC-mediated integration into naked DNA but blocked integration into nucleosomes. The block for the PIC-mediated integration was significantly relieved by H3K36me3 modification. Mapping the integration sites in the preferred substrates revealed that specific features of the nucleosome-bound DNA are preferred for integration, whereas integration into naked DNA was random. Finally, biochemical and genetic studies demonstrate that DNA condensation by the H1 protein dramatically reduces integration, providing further evidence that features inherent to the open chromatin are preferred for HIV-1 integration. Collectively, these results identify the optimal target substrate for HIV-1 integration, report a mechanistic link between H3K36me3 and integration preference, and importantly, reveal distinct mechanisms utilized by the PIC for integration compared to the intasomes.

Indexed as

Chromosomes, HumanHistone CodeHistonesHIV-1NucleosomesVirus IntegrationChromatinDNA, ViralHIV InfectionsHIV IntegraseHumansLysineMethylationChromatinDNA, ViralHistonesHIV IntegraseLysineNucleosomeschromatinH3K36me3histoneHIVhuman immunodeficiency virusintasomeintegrationnucleosomePICposttranslational modificationpreintegration complexPTM

Identifiers

PMID36094316
PMCPMC9517705

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.