Evidence map›Paper›PMID 26900410›Full record

ArticleClinical epigenetics2016

Development of 5' LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals.

Kateřina Trejbalová, Denisa Kovářová, Jana Blažková, Ladislav Machala, David Jilich, Jan Weber, Dana Kučerová, Ondřej Vencálek, Ivan Hirsch, Jiří Hejnar

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
5.0field-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

45 citing papers in PubMed, 63 citations in OpenAlex.

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  18. Deciphering DNA Methylation in HIV Infection.Frontiers in immunology · 2021
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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

10 authors at 6 institutions in 1 country.

Kateřina TrejbalováInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-14220 Prague 4, Czech Republic.
Denisa KovářováInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-14220 Prague 4, Czech Republic.
Jana BlažkováInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-14220 Prague 4, Czech Republic.
Ladislav MachalaDepartment of Infectious Diseases, Third Faculty of Medicine, Charles University and Hospital Na Bulovce in Prague, Budínova 67/2, CZ-18081 Prague 8, Czech Republic.
David JilichDepartment of Infectious, Tropical and Parasitic Diseases, First Faculty of Medicine, Charles University in Prague and Hospital Na Bulovce, Budínova 67/ 2, CZ-18081 Prague 8, Czech Republic.
Jan WeberInstitute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, CZ-16610 Prague 6, Czech Republic.
Dana KučerováInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-14220 Prague 4, Czech Republic.
Ondřej VencálekDepartment of Mathematical Analysis and Applications of Mathematics, Faculty of Science of the Palacky University in Olomouc, Olomouc, CZ-77146 Czech Republic.
Ivan HirschInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-14220 Prague 4, Czech Republic ; Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, CZ-16610 Prague 6, Czech Republic ; Faculty of Science, Department of Genetics and Microbiology, Charles University in Prague, Viničná 5, CZ-12844 Prague 2, Czech Republic ; Inserm, Centre de Recherche en Cancérologie de Marseille (CRCM), F-13273 Marseille, France ; Institut Paoli-Calmettes, F-13009 Marseille, France ; Aix-Marseille Univ., F-13284 Marseille, France ; CNRS, UMR7258, CRCM, F-13009 Marseille, France.
Jiří HejnarInstitute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, CZ-14220 Prague 4, Czech Republic.
Czech Academy of Sciences · CZCzech Academy of Sciences, Institute of Molecular Genetics · CZCzech Academy of Sciences, Institute of Organic Chemistry and Biochemistry · CZCharles University · CZFakultní nemocnice Bulovka · CZPalacký University Olomouc · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHuman immunodeficiency virus type 1 (HIV-1) latency represents the major barrier to virus eradication in infected individuals because cells harboring latent HIV-1 provirus are not affected by current antiretroviral therapy (ART). We previously demonstrated that DNA methylation of HIV-1 long terminal repeat (5' LTR) restricts HIV-1 reactivation and, together with chromatin conformation, represents an important mechanism of HIV-1 latency maintenance. Here, we explored the new issue of temporal development of DNA methylation in latent HIV-1 5' LTR.

resultsIn the Jurkat CD4(+) T cell model of latency, we showed that the stimulation of host cells contributed to de novo DNA methylation of the latent HIV-1 5' LTR sequences. Consecutive stimulations of model CD4(+) T cell line with TNF-α and PMA or with SAHA contributed to the progressive accumulation of 5' LTR DNA methylation. Further, we showed that once established, the high DNA methylation level of the latent 5' LTR in the cell line model was a stable epigenetic mark. Finally, we explored the development of 5' LTR DNA methylation in the latent reservoir of HIV-1-infected individuals who were treated with ART. We detected low levels of 5' LTR DNA methylation in the resting CD4(+) T cells of the group of patients who were treated for up to 3 years. However, after long-term ART, we observed an accumulation of 5' LTR DNA methylation in the latent reservoir. Importantly, within the latent reservoir of some long-term-treated individuals, we uncovered populations of proviral molecules with a high density of 5' LTR CpG methylation.

conclusionsOur data showed the presence of 5' LTR DNA methylation in the long-term reservoir of HIV-1-infected individuals and implied that the transient stimulation of cells harboring latent proviruses may contribute, at least in part, to the methylation of the HIV-1 promoter.

Indexed as

DNA MethylationAnti-HIV AgentsAntiretroviral Therapy, Highly ActiveCell LineFemaleHIV-1HIV InfectionsHIV Long Terminal RepeatHumansJurkat CellsMaleProvirusesTime FactorsVirus LatencyAnti-HIV AgentsChromatin conformationDNA methylationHIV-1HIV-1-infected individualsLatent HIV-1 provirus reactivationLatent reservoir

Identifiers

PMID26900410
PMCPMC4759744
OpenAlexW2287627428

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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.