Evidence map›Paper›PMID 29977044›Full record

ArticleScientific reports2018

Spontaneous reactivation of latent HIV-1 promoters is linked to the cell cycle as revealed by a genetic-insulators-containing dual-fluorescence HIV-1-based vector.

Yik Lim Kok, Stefan Schmutz, Anne Inderbitzin, Kathrin Neumann, Audrey Kelley, Lisa Jörimann, Mohaned Shilaih, Valentina Vongrad, Roger D Kouyos, Huldrych F Günthard and 2 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

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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

12 authors at 2 institutions in 2 countries.

Yik Lim KokDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Stefan SchmutzInstitute of Medical Virology, University of Zurich, Zurich, Switzerland.
Anne InderbitzinDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Kathrin NeumannDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Audrey KelleyDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Lisa JörimannDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Mohaned ShilaihDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Valentina VongradDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Roger D KouyosDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.
Huldrych F GünthardDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.ORCID 0000-0002-1142-6723
Christian BerensInstitute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, Jena, Germany.ORCID 0000-0002-7500-5864
Karin J MetznerDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland. karin.metzner@usz.ch.
University of Zurich · CHFriedrich-Loeffler-Institut · DE

Funding

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 310030_141067
6 · The paper itself

Abstract

Long-lived latently HIV-1-infected cells represent a barrier to cure. We developed a dual-fluorescence HIV-1-based vector containing a pair of genetic insulators flanking a constitutive fluorescent reporter gene to study HIV-1 latency. The protective effects of these genetic insulators are demonstrated through long-term (up to 394 days) stable fluorescence profiles in transduced SUP-T1 cells. Analysis of 1,941 vector integration sites confirmed reproduction of HIV-1 integration patterns. We sorted monoclonal cells representing latent HIV-1 infections and found that both vector integration sites and integrity of the vector genomes influence the reactivation potentials of latent HIV-1 promoters. Interestingly, some latent monoclonal cells exhibited a small cell subpopulation with a spontaneously reactivated HIV-1 promoter. Higher expression levels of genes involved in cell cycle progression are observed in these cell subpopulations compared to their counterparts with HIV-1 promoters that remained latent. Consistently, larger fractions of spontaneously reactivated cells are in the S and G2 phases of the cell cycle. Furthermore, genistein and nocodazole treatments of these cell clones, which halted cells in the G2 phase, resulted in a 1.4-2.9-fold increase in spontaneous reactivation. Taken together, our HIV-1 latency model reveals that the spontaneous reactivation of latent HIV-1 promoters is linked to the cell cycle.

Indexed as

Promoter Regions, GeneticVirus ActivationCell CycleCell LineClone CellsGenes, ReporterGenisteinHIV-1HIV InfectionsHumansNocodazoleTransduction, GeneticVirus IntegrationVirus LatencyGenisteinNocodazole

Identifiers

PMID29977044
PMCPMC6033903
OpenAlexW2809883665

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.