Evidence map›Paper›PMID 38110433›Full record

ArticleNature communications2023

Potent latency reversal by Tat RNA-containing nanoparticle enables multi-omic analysis of the HIV-1 reservoir.

Marion Pardons, Basiel Cole, Laurens Lambrechts, Willem van Snippenberg, Sofie Rutsaert, Ytse Noppe, Nele De Langhe, Annemieke Dhondt, Jerel Vega, Filmon Eyassu and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing 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

34 citing papers in PubMed, 35 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

14 authors at 3 institutions in 3 countries.

Marion Pardons *HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, 9000, Ghent, Belgium.ORCID 0000-0002-9921-8207
Basiel Cole *HIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, 9000, Ghent, Belgium.
Laurens LambrechtsHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, 9000, Ghent, Belgium.ORCID 0000-0002-1415-4591
Willem van SnippenbergHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, 9000, Ghent, Belgium.ORCID 0000-0001-8903-3631
Sofie RutsaertHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, 9000, Ghent, Belgium.
Ytse NoppeHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, 9000, Ghent, Belgium.
Nele De LangheHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, 9000, Ghent, Belgium.
Annemieke DhondtDepartment of Nephrology, Ghent University Hospital, 9000, Ghent, Belgium.
Jerel VegaArcturus Therapeutics, 10628 Science Center Drive, Suite 250, San Diego, 92121, CA, USA.
Filmon EyassuComputational biology, Johnson and Johnson, 2340, Beerse, Belgium.
Erik NijsJanssen infectious diseases and diagnostics, Johnson and Johnson, 2340, Beerse, Belgium.
Ellen Van GulckJanssen infectious diseases and diagnostics, Johnson and Johnson, 2340, Beerse, Belgium.
Daniel BodenJanssen Biopharma, Johnson and Johnson, South San Francisco, 94080, CA, USA.
Linos VandekerckhoveHIV Cure Research Center, Department of Internal Medicine and Pediatrics, Ghent University Hospital, Ghent University, 9000, Ghent, Belgium. linos.vandekerckhove@ugent.be.ORCID 0000-0002-8600-1631
Ghent University Hospital · BEJohnson & Johnson (United States) · USArcturus Therapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The development of latency reversing agents that potently reactivate HIV without inducing global T cell activation would benefit the field of HIV reservoir research and could pave the way to a functional cure. Here, we explore the reactivation capacity of a lipid nanoparticle containing Tat mRNA (Tat-LNP) in CD4 T cells from people living with HIV undergoing antiretroviral therapy (ART). When combined with panobinostat, Tat-LNP induces latency reversal in a significantly higher proportion of latently infected cells compared to PMA/ionomycin (≈ 4-fold higher). We demonstrate that Tat-LNP does not alter the transcriptome of CD4 T cells, enabling the characterization of latently infected cells in their near-native state. Upon latency reversal, we identify transcriptomic differences between infected cells carrying an inducible provirus and non-infected cells (e.g. LINC02964, GZMA, CCL5). We confirm the transcriptomic differences at the protein level and provide evidence that the long non-coding RNA LINC02964 plays a role in active HIV infection. Furthermore, p24+ cells exhibit heightened PI3K/Akt signaling, along with downregulation of protein translation, suggesting that HIV-infected cells display distinct signatures facilitating their long-term persistence. Tat-LNP represents a valuable research tool for in vitro reservoir studies as it greatly facilitates the in-depth characterization of HIV reservoir cells' transcriptome and proteome profiles.

Indexed as

Gene Products, tatHIV-1NanoparticlesRNA, ViralVirus LatencyAntiretroviral Therapy, Highly ActiveCD4 AntigensCD4-Positive T-LymphocytesCells, CulturedHIV Core Protein p24HIV InfectionsHumansIonomycinPanobinostatProvirusesRNA, Long NoncodingCD4 AntigensGene Products, tatHIV Core Protein p24IonomycinPanobinostatRNA, Long NoncodingRNA, Viral

Identifiers

PMID38110433
PMCPMC10728105
OpenAlexW4389894071

What OpenQuestion holds

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LicenceCC BY
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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.