Evidence map›Paper›PMID 26502902›Full record

ArticleRetrovirology2015

Latent HIV-1 is activated by exosomes from cells infected with either replication-competent or defective HIV-1.

Claudia Arenaccio, Simona Anticoli, Francesco Manfredi, Chiara Chiozzini, Eleonora Olivetta, Maurizio Federico

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

68 citing papers in PubMed, 88 citations in OpenAlex.

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  17. Extracellular Vesicles and Their Use as Vehicles of Immunogens.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  18. Review
  19. Review
  20. The reservoir of latent HIV.Frontiers in cellular and infection microbiology · 2022
    Review

8 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

6 authors at 1 institution in 1 country.

Claudia ArenaccioNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. claudia.arenaccio@guest.iss.it.
Simona AnticoliNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. simona.anticoli@iss.it.
Francesco ManfrediNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. francesco.manfredi@iss.it.
Chiara ChiozziniNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. chiara.chiozzini@iss.it.
Eleonora OlivettaNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. eleonora.olivetta@iss.it.
Maurizio FedericoNational AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy. maurizio.federico@iss.it.
Istituto Superiore di Sanità · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundCompletion of HIV life cycle in CD4(+) T lymphocytes needs cell activation. We recently reported that treatment of resting CD4(+) T lymphocytes with exosomes produced by HIV-1 infected cells induces cell activation and susceptibility to HIV replication. Here, we present data regarding the effects of these exosomes on cells latently infected with HIV-1.

resultsHIV-1 latently infecting U937-derived U1 cells was activated upon challenge with exosomes purified from the supernatant of U937 cells chronically infected with HIV-1. This effect was no more detectable when exosomes from cells infected with HIV-1 strains either nef-deleted or expressing a functionally defective Nef were used, indicating that Nef is the viral determinant of exosome-induced HIV-1 activation. Treatment with either TAPI-2, i.e., a specific inhibitor of the pro-TNFα-processing ADAM17 enzyme, or anti-TNFα Abs abolished HIV-1 activation. Hence, similar to what previously demonstrated for the exosome-mediated activation of uninfected CD4(+) T lymphocytes, the Nef-ADAM17-TNFα axis is part of the mechanism of latent HIV-1 activation. It is noteworthy that these observations have been reproduced using: (1) primary CD4(+) T lymphocytes latently infected with HIV-1; (2) exosomes from both primary CD4(+) T lymphocytes and macrophages acutely infected with HIV-1; (3) co-cultures of HIV-1 acutely infected CD4(+) T lymphocytes and autologous lymphocytes latently infected with HIV-1, and (4) exosomes from cells expressing a defective HIV-1.

conclusionsOur results strongly suggest that latent HIV-1 can be activated by TNFα released by cells upon ingestion of exosomes released by infected cells, and that this effect depends on the activity of exosome-associated ADAM17. These pieces of evidence shed new light on the mechanism of HIV reactivation in latent reservoirs, and might also be relevant to design new therapeutic interventions focused on HIV eradication.

Indexed as

Virus ActivationVirus LatencyADAM17 ProteinADAM ProteinsCD4-Positive T-LymphocytesCells, CulturedCoculture TechniquesExosomesHIV-1HumansHydroxamic Acidsnef Gene Products, Human Immunodeficiency VirusTumor Necrosis Factor-alphaU937 CellsVirus ReplicationADAM17 ProteinADAM17 protein, humanADAM ProteinsHydroxamic Acidsnef Gene Products, Human Immunodeficiency VirusTAPI-2TNF protein, humanTumor Necrosis Factor-alpha

Identifiers

PMID26502902
PMCPMC4623921
OpenAlexW2102099730

What OpenQuestion holds

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LicenceCC BY
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.