Evidence map›Paper›PMID 30615681›Full record

ArticlePLoS pathogens2019

Epstein-Barr virus microRNAs regulate B cell receptor signal transduction and lytic reactivation.

Yan Chen, Devin Fachko, Nikita S Ivanov, Camille M Skinner, Rebecca L Skalsky

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
3.8field-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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Pooled it
  2. Virulence · 2026
    Article
  3. Reconstructing EBV reactivation and DNA damage response kinetics in morphologic pseudotime.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  14. Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025
    Review
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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

5 authors at 1 institution in 1 country.

Yan ChenVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.
Devin FachkoVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0003-1646-8102
Nikita S IvanovVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0002-9187-7582
Camille M SkinnerVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0002-4062-7487
Rebecca L SkalskyVaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, Oregon, United States of America.ORCID 0000-0003-2967-9478
Oregon Health & Science University · US

Funding

The Role of Viral and Cellular miRNAs in B-cell LymphomagenesisR00CA175181 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI SKALSKY, REBECCA L · 2016 to 2018
$717k
The role of viral and cellular miRNAs in B-cell lymphomagenesisK99CA175181 · NCI · OREGON HEALTH & SCIENCE UNIVERSITY · PI SKALSKY, REBECCA L · 2014 to 2015
$199k
NCI NIH HHS K99 CA175181NCI NIH HHS R00 CA175181
6 · The paper itself

Abstract

MicroRNAs (miRNAs) are post-transcriptional regulatory RNAs that can modulate cell signaling and play key roles in cell state transitions. Epstein-Barr virus (EBV) expresses >40 viral miRNAs that manipulate both viral and cellular gene expression patterns and contribute to reprogramming of the host environment during infection. Here, we identified a subset of EBV miRNAs that desensitize cells to B cell receptor (BCR) stimuli, and attenuate the downstream activation of NF-kappaB or AP1-dependent transcription. Bioinformatics and pathway analysis of Ago PAR-CLIP datasets identified multiple EBV miRNA targets related to BCR signal transduction, including GRB2, SOS1, MALT1, RAC1, and INPP5D, which we validated in reporter assays. BCR signaling is critical for B cell activation, proliferation, and differentiation, and for EBV, is linked to reactivation. In functional assays, we demonstrate that EBV miR-BHRF1-2-5p contributes to the growth of latently infected B cells through GRB2 regulation. We further determined that activities of EBV miR-BHRF1-2-5p, EBV miR-BART2-5p, and a cellular miRNA, miR-17-5p, directly regulate virus reactivation triggered by BCR engagement. Our findings provide mechanistic insight into some of the key miRNA interactions impacting the proliferation of latently infected B cells and importantly, governing the latent to lytic switch.

Indexed as

B-LymphocytesCell LineEpstein-Barr Virus InfectionsGene Expression Regulation, ViralGRB2 Adaptor ProteinHEK293 CellsHerpesvirus 4, HumanHumansMicroRNAsNF-kappa BReceptors, Antigen, B-CellSignal TransductionViral ProteinsVirus LatencyGRB2 Adaptor ProteinGRB2 protein, humanMicroRNAsNF-kappa BReceptors, Antigen, B-CellViral Proteins

Identifiers

PMID30615681
PMCPMC6336353
OpenAlexW2908235148

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.