Evidence map›Paper›PMID 32575590›Full record

ArticleViruses2020

Extracellular Vesicle Activation of Latent HIV-1 Is Driven by EV-Associated c-Src and Cellular SRC-1 via the PI3K/AKT/mTOR Pathway.

Robert A Barclay, Gifty A Mensah, Maria Cowen, Catherine DeMarino, Yuriy Kim, Daniel O Pinto, James Erickson, Fatah Kashanchi

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 21% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Article
  9. Article
  10. Occludin: a gatekeeper of brain Infection by HIV-1.Fluids and barriers of the CNS · 2023
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. CounterAKTing HIV: Toward a "Block and Clear" Strategy?Frontiers in cellular and infection microbiology · 2022
    Review
  17. Review
  18. Review
  19. Review
  20. Article
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

8 authors at 1 institution in 1 country.

Robert A BarclayLaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA.
Gifty A MensahLaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA.
Maria CowenLaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA.
Catherine DeMarinoLaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA.
Yuriy KimLaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA.
Daniel O PintoLaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA.
James EricksonLaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA.
Fatah KashanchiLaboratory of Molecular Virology, George Mason University, Manassas, VA 20110, USA.
George Mason University · US

Funding

HIV neuropathogenesis related to exosomes containing HIV non-coding RNAsR01NS099029 · NINDS · GEORGE MASON UNIVERSITY · PI KASHANCHI, FATAH · 2016 to 2020
$1.9M
NIH HHS AI043894NIH HHS AI074410NIH HHS AI078859NIH HHS AI127351-01NIH HHS NS099029NINDS NIH HHS R01 NS099029
6 · The paper itself

Abstract

HIV-1 is a global health crisis that has infected more than 37 million people. Latent reservoirs throughout the body are a major hurdle when it comes to eradicating the virus. In our previous study, we found that exosomes, a type of extracellular vesicle (EV), from uninfected cells activate the transcription of HIV-1 in latent infected cells, regardless of combination antiretroviral therapy (cART). In this study, we investigated the specific mechanism behind the EV activation of latent HIV-1. We found that phosphorylated c-Src is present in EVs of various cell lines and has the ability to activate downstream proteins such as EGFR, initiating a signal cascade. EGFR is then able to activate the PI3K/AKT/mTOR pathway, resulting in the activation of STAT3 and SRC-1, culminating in the reversal of HIV-1 latency. This was verified by examining levels of HIV-1 TAR, genomic RNA and HIV-1 Gag p24 protein in cell lines and primary cells. We found that EVs containing c-Src rescued HIV-1 despite the presence of inhibitors, validating the importance of EV-associated c-Src in latent HIV-1 activation. Lastly, we discovered an increased recruitment of p300 and NF-κB in the nucleus of EV-treated infected cells. Collectively, our data suggest that EV-associated c-Src is able to activate latent HIV-1 via the PI3K/AKT/mTOR pathway and SRC-1/p300-driven chromatin remodeling. These findings could aid in designing new strategies to prevent the reactivation of latent HIV-1 in patients under cART.

Indexed as

Cell Line, TumorE1A-Associated p300 ProteinErbB ReceptorsExosomesExtracellular VesiclesHIV-1HIV Core Protein p24HIV InfectionsHumansJurkat CellsNF-kappa BPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins pp60(c-src)RNA-Binding ProteinsSTAT3 Transcription FactorE1A-Associated p300 ProteinEGFR protein, humanEP300 protein, humanErbB ReceptorsHIV Core Protein p24MTOR protein, humanNF-kappa Bp24 protein, Human Immunodeficiency Virus Type 1Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins pp60(c-src)RNA-Binding ProteinsSTAT3 protein, humanSTAT3 Transcription FactorTOR Serine-Threonine Kinasesc-Srcextracellular vesicleHIV-1PI3/AKT/mTOR pathwaySRC-1

Identifiers

PMID32575590
PMCPMC7354524
OpenAlexW3036336395

What OpenQuestion holds

Textmetadata
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.