Evidence map›Paper›PMID 20304794›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2010

Functional delivery of viral miRNAs via exosomes.

D Michiel Pegtel, Katherine Cosmopoulos, David A Thorley-Lawson, Monique A J van Eijndhoven, Erik S Hopmans, Jelle L Lindenberg, Tanja D de Gruijl, Thomas Würdinger, Jaap M Middeldorp

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 932 papers.

0numbers the graph read from it
0cells of the map it votes in
932citing papers in PubMed
–field-weighted citation impact
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

932 citing papers in PubMed.

  1. Trial
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  14. Rethinking Extracellular Vesicle Signaling.Advanced materials (Deerfield Beach, Fla.) · 2026
    Article
  15. Dengue virus harnesses mosquito Syntenin to load and secrete viral RNA into salivary exosomes.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

872 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

9 authors.

D Michiel PegtelDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit University Medical Center, 1081HV Amsterdam, The Netherlands. d.pegtel@vumc.nl
Katherine Cosmopoulos
David A Thorley-Lawson
Monique A J van Eijndhoven
Erik S Hopmans
Jelle L Lindenberg
Tanja D de Gruijl
Thomas Würdinger
Jaap M Middeldorp

Funding

EPSTEIN BARR VIRUS LATENCYR01CA065883 · NCI · TUFTS UNIVERSITY BOSTON · PI THORLEY-LAWSON, DAVID A. · 1995 to 2014
$4.3M
NCI NIH HHS R01 CA065883
6 · The paper itself

Abstract

Noncoding regulatory microRNAs (miRNAs) of cellular and viral origin control gene expression by repressing the translation of mRNAs into protein. Interestingly, miRNAs are secreted actively through small vesicles called "exosomes" that protect them from degradation by RNases, suggesting that these miRNAs may function outside the cell in which they were produced. Here we demonstrate that miRNAs secreted by EBV-infected cells are transferred to and act in uninfected recipient cells. Using a quantitative RT-PCR approach, we demonstrate that mature EBV-encoded miRNAs are secreted by EBV-infected B cells through exosomes. These EBV-miRNAs are functional because internalization of exosomes by MoDC results in a dose-dependent, miRNA-mediated repression of confirmed EBV target genes, including CXCL11/ITAC, an immunoregulatory gene down-regulated in primary EBV-associated lymphomas. We demonstrate that throughout coculture of EBV-infected B cells EBV-miRNAs accumulate in noninfected neighboring MoDC and show that this accumulation is mediated by transfer of exosomes. Thus, the exogenous EBV-miRNAs transferred through exosomes are delivered to subcellular sites of gene repression in recipient cells. Finally, we show in peripheral blood mononuclear cells from patients with increased EBV load that, although EBV DNA is restricted to the circulating B-cell population, EBV BART miRNAs are present in both B-cell and non-B-cell fractions, suggestive of miRNA transfer. Taken together our findings are consistent with miRNA-mediated gene silencing as a potential mechanism of intercellular communication between cells of the immune system that may be exploited by the persistent human gamma-herpesvirus EBV.

Indexed as

B-LymphocytesCells, CulturedCoculture TechniquesDendritic CellsExosomesHerpesvirus 4, HumanHumansMicroRNAsMicroscopy, ElectronRNA, ViralVirus InternalizationMicroRNAsRNA, Viral

Identifiers

PMID20304794
PMCPMC2851954

What OpenQuestion holds

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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.