Evidence map›Paper›PMID 26553869›Full record

ArticleThe Journal of biological chemistry2016

Exosomes from HIV-1-infected Cells Stimulate Production of Pro-inflammatory Cytokines through Trans-activating Response (TAR) RNA.

Gavin C Sampey, Mohammed Saifuddin, Angela Schwab, Robert Barclay, Shreya Punya, Myung-Chul Chung, Ramin M Hakami, Mohammad Asad Zadeh, Benjamin Lepene, Zachary A Klase and 4 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed
9.5field-weighted citation impact, top 1% 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

159 citing papers in PubMed, 206 citations in OpenAlex.

  1. Review
  2. Biology and Therapeutic Potential of Exosomes, Targeted Drug Delivery.International journal of molecular sciences · 2026
    Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Extracellular vesicles in viral disease management.Current research in microbial sciences · 2026
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. The Role of Extracellular Vesicles in Pandemic Viral Infections.Journal of microbiology (Seoul, Korea) · 2024
    Review
  20. Article

99 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

14 authors at 5 institutions in 1 country.

Gavin C SampeyFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110.
Mohammed SaifuddinFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110.
Angela SchwabFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110.
Robert BarclayFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110.
Shreya PunyaFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110.
Myung-Chul ChungFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110.
Ramin M HakamiFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110.ORCID http://orcid.org/0000-0001-7122-0164
Mohammad Asad ZadehFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110.
Benjamin LepeneCeres Nanosciences Inc., Manassas, Virginia 20110.
Zachary A Klasethe Department of Biological Sciences, University of the Sciences, Philadelphia, Pennsylvania 19104.
Nazira El-Hagethe Department of Immunology, Herbert Wertheim College of Medicine, Miami, Florida 33199, and.
Mary Youngthe Department of Medicine, Women's Intra-Agency HIV Study, Georgetown University, Washington, D. C. 20007.
Sergey IordanskiyFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110, siordans@gmu.edu.
Fatah KashanchiFrom the Laboratory of Molecular Virology, George Mason University, Manassas, Virginia 20110, fkashanc@gmu.edu.
George Mason University · USCeres Nanosciences · USDr. Herbert & Nicole Wertheim Family Foundation · USGeorgetown University · USUniversity of the Sciences · US

Funding

WOMEN'S INTERAGENCY HIV STUDY (WIHS) ORGANIZATION AND MANAGEMENTU01AI034994 · NIAID · GEORGETOWN UNIVERSITY · PI KASSAYE, SEBLE G · 1993 to 2018
$52.0M
HIV1 INHIBITION USING TAT PEPTIDE DERIVATIVESR01AI043894 · NIAID · UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL · PI KASHANCHI, FATAH · 1999 to 2015
$4.4M
HIV neuropathogenesis related to exosomes containing HIV non-coding RNAsR01NS099029 · NINDS · GEORGE MASON UNIVERSITY · PI KASHANCHI, FATAH · 2016 to 2020
$1.9M
Effect of chromatin remodelers/modifiers on HIV-1 Tat activated transcriptionR21AI074410 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI KASHANCHI, FATAH · 2009 to 2010
$432k
Nanotrap particle-based assay to quantify HIV-1 in latently-infected T cellsR21AI113140 · NIAID · GEORGE MASON UNIVERSITY · PI KASHANCHI, FATAH · 2014 to 2015
$409k
HIV-1 TAR derived miRNA: Implications for Latency and PathogenesisR21AI078859 · NIAID · GEORGE WASHINGTON UNIVERSITY · PI KASHANCHI, FATAH · 2009 to 2010
$400k
Effects of Exosomes Derived from HIV-1 Infected Cells on Viral SpreadF31NS086453 · NINDS · GEORGE MASON UNIVERSITY · PI SAMPEY, GAVIN · 2014 to 2015
$40k
NIAID NIH HHS AI043894NIAID NIH HHS AI074410NIAID NIH HHS AI078859NIAID NIH HHS R01 AI043894NIAID NIH HHS R21 AI074410NIAID NIH HHS R21 AI078859NIAID NIH HHS R21 AI113140NIAID NIH HHS U01 AI034994NINDS NIH HHS F31 NS086453NINDS NIH HHS NS086453NINDS NIH HHS R01 NS099029
6 · The paper itself

Abstract

HIV-1 infection results in a chronic illness because long-term highly active antiretroviral therapy can lower viral titers to an undetectable level. However, discontinuation of therapy rapidly increases virus burden. Moreover, patients under highly active antiretroviral therapy frequently develop various metabolic disorders, neurocognitive abnormalities, and cardiovascular diseases. We have previously shown that exosomes containing trans-activating response (TAR) element RNA enhance susceptibility of undifferentiated naive cells to HIV-1 infection. This study indicates that exosomes from HIV-1-infected primary cells are highly abundant with TAR RNA as detected by RT-real time PCR. Interestingly, up to a million copies of TAR RNA/μl were also detected in the serum from HIV-1-infected humanized mice suggesting that TAR RNA may be stable in vivo. Incubation of exosomes from HIV-1-infected cells with primary macrophages resulted in a dramatic increase of proinflammatory cytokines, IL-6 and TNF-β, indicating that exosomes containing TAR RNA could play a direct role in control of cytokine gene expression. The intact TAR molecule was able to bind to PKR and TLR3 effectively, whereas the 5' and 3' stems (TAR microRNAs) bound best to TLR7 and -8 and none to PKR. Binding of TAR to PKR did not result in its phosphorylation, and therefore, TAR may be a dominant negative decoy molecule in cells. The TLR binding through either TAR RNA or TAR microRNA potentially can activate the NF-κB pathway and regulate cytokine expression. Collectively, these results imply that exosomes containing TAR RNA could directly affect the proinflammatory cytokine gene expression and may explain a possible mechanism of inflammation observed in HIV-1-infected patients under cART.

Indexed as

Activating Transcription FactorsActive Transport, Cell NucleusAnimalsCell LineCell Line, TransformedCells, CulturedCell Transformation, ViralCytokineseIF-2 KinaseExosomesHIV-1HIV InfectionsHumansInterleukin-6LeukocytesLymphotoxin-alphaActivating Transcription FactorsCytokineseIF-2 KinaseIL6 protein, humanInterleukin-6Lymphotoxin-alphaMicroRNAsTLR3 protein, humanToll-Like Receptor 3cytokinesisexosome (vesicle)human immunodeficiency virus (HIV)macrophageprotein kinase RNA-activated (PKR)TAR RNAtoll-like receptor (TLR)

Identifiers

PMID26553869
PMCPMC4714213
OpenAlexW2237018933

What OpenQuestion holds

Textmetadata
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.