Evidence map›Paper›PMID 26768848›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Sensing of latent EBV infection through exosomal transfer of 5'pppRNA.

S Rubina Baglio, Monique A J van Eijndhoven, Danijela Koppers-Lalic, Jordi Berenguer, Sinéad M Lougheed, Susan Gibbs, Nicolas Léveillé, Rico N P M Rinkel, Erik S Hopmans, Sankar Swaminathan and 14 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
15.5field-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

109 citing papers in PubMed, 160 citations in OpenAlex.

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  20. Viruses · 2024
    Review

49 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

24 authors at 6 institutions in 3 countries.

S Rubina BaglioDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit (VU) University Medical Center, 1081 HV Amsterdam, The Netherlands;
Monique A J van EijndhovenDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit (VU) University Medical Center, 1081 HV Amsterdam, The Netherlands;
Danijela Koppers-LalicDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit (VU) University Medical Center, 1081 HV Amsterdam, The Netherlands; Department of Neurosurgery, Cancer Center Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Jordi BerenguerDepartment of Neurosurgery, Cancer Center Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Sinéad M LougheedDepartment of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Susan GibbsDepartment of Dermatology, Cancer Center Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands; Department of Oral Cell Biology, Academic Center for Dentistry Amsterdam, University of Amsterdam and VU University, 1081 HZ Amsterdam, The Netherlands;
Nicolas LéveilléLaboratory for Experimental Oncology and Radiobiology, Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), 1105 AZ Amsterdam, The Netherlands;
Rico N P M RinkelDepartment of Otolaryngology, Cancer Center Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Erik S HopmansDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit (VU) University Medical Center, 1081 HV Amsterdam, The Netherlands;
Sankar SwaminathanDepartment of Medicine, University of Utah and George E. Wahlen VA Medical Center, Salt Lake City, UT 84132;
Sandra A W M VerkuijlenDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit (VU) University Medical Center, 1081 HV Amsterdam, The Netherlands;
George L SchefferDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit (VU) University Medical Center, 1081 HV Amsterdam, The Netherlands;
Frank J M van KuppeveldDepartment of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University Hospital, 3584 CL Utrecht, The Netherlands;
Tanja D de GruijlDepartment of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Irene E M BultinkDepartment of Rheumatology, Amsterdam Rheumatology and Immunology Center, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Ekaterina S JordanovaDepartment of Obstetrics and Gynecology, Center for Gynaecological Oncology Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Michael HackenbergDepartment of Genetics, University of Granada, 18071 Granada, Spain;
Sander R PiersmaDepartment of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
Jaco C KnolDepartment of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
Alexandre E VoskuylDepartment of Rheumatology, Amsterdam Rheumatology and Immunology Center, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Thomas WurdingerDepartment of Neurosurgery, Cancer Center Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands;
Connie R JiménezDepartment of Medical Oncology, Cancer Center Amsterdam, VU University Medical Center, 1081 HV Amsterdam, The Netherlands.
Jaap M MiddeldorpDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit (VU) University Medical Center, 1081 HV Amsterdam, The Netherlands;
D Michiel PegtelDepartment of Pathology, Cancer Center Amsterdam, Vrije Universiteit (VU) University Medical Center, 1081 HV Amsterdam, The Netherlands; d.pegtel@vumc.nl.
Amsterdam UMC Location VUmc · NLAcademic Center for Dentistry Amsterdam · NLAcademic Medical Center · NLGeorge E. Wahlen Department of VA Medical Center · USUniversidad de Granada · ESUtrecht University · NL

Funding

Restriction of Oncogenic Herpesviruses by Host Cell FactorsI01BX002262 · VA · VA SALT LAKE CITY HEALTHCARE SYSTEM · PI SWAMINATHAN, SANKAR · 2015 to 2019
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Worldwide Cancer Research 11-0157
6 · The paper itself

Abstract

Complex interactions between DNA herpesviruses and host factors determine the establishment of a life-long asymptomatic latent infection. The lymphotropic Epstein-Barr virus (EBV) seems to avoid recognition by innate sensors despite massive transcription of immunostimulatory small RNAs (EBV-EBERs). Here we demonstrate that in latently infected B cells, EBER1 transcripts interact with the lupus antigen (La) ribonucleoprotein, avoiding cytoplasmic RNA sensors. However, in coculture experiments we observed that latent-infected cells trigger antiviral immunity in dendritic cells (DCs) through selective release and transfer of RNA via exosomes. In ex vivo tonsillar cultures, we observed that EBER1-loaded exosomes are preferentially captured and internalized by human plasmacytoid DCs (pDCs) that express the TIM1 phosphatidylserine receptor, a known viral- and exosomal target. Using an EBER-deficient EBV strain, enzymatic removal of 5'ppp, in vitro transcripts, and coculture experiments, we established that 5'pppEBER1 transfer via exosomes drives antiviral immunity in nonpermissive DCs. Lupus erythematosus patients suffer from elevated EBV load and activated antiviral immunity, in particular in skin lesions that are infiltrated with pDCs. We detected high levels of EBER1 RNA in such skin lesions, as well as EBV-microRNAs, but no intact EBV-DNA, linking non-cell-autonomous EBER1 presence with skin inflammation in predisposed individuals. Collectively, our studies indicate that virus-modified exosomes have a physiological role in the host-pathogen stand-off and may promote inflammatory disease.

Indexed as

Biological TransportDendritic CellsEpstein-Barr Virus InfectionsExosomesHerpesvirus 4, HumanHumansProteomeRNA, Viral5'PPP-RNAProteomeRNA, Viraldendritic cellsEBV-EBER1exosomesinnate sensingskin inflammation

Identifiers

PMID26768848
PMCPMC4747727
OpenAlexW2235539081

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.