Evidence map›Paper›PMID 27974566›Full record

ArticleJournal of virology2017

CD63 Regulates Epstein-Barr Virus LMP1 Exosomal Packaging, Enhancement of Vesicle Production, and Noncanonical NF-κB Signaling.

Stephanie N Hurwitz, Dingani Nkosi, Meghan M Conlon, Sara B York, Xia Liu, Deanna C Tremblay, David G Meckes

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.

0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed
9.4field-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

134 citing papers in PubMed, 194 citations in OpenAlex.

  1. Article
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  6. Review
  7. The Role of Extracellular Vesicles in Epstein-Barr Virus Immunology and Pathogenesis for Possible Diagnostic and Therapeutic Direction.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026
    Review
  8. Article
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74 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

7 authors at 1 institution in 1 country.

Stephanie N HurwitzDepartment of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, USA.
Dingani NkosiDepartment of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, USA.
Meghan M ConlonDepartment of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, USA.
Sara B YorkDepartment of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, USA.
Xia LiuDepartment of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, USA.
Deanna C TremblayDepartment of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, USA.
David G MeckesDepartment of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, Florida, USA david.meckes@med.fsu.edu.
Florida State University · US

Funding

Modulation of Host Cell Exosome Content and Function by EBV LMP1R01CA204621 · NCI · FLORIDA STATE UNIVERSITY · PI MECKES, DAVID G · 2016 to 2020
$2.2M
Exosome-Dependent Trafficking of Epstein-Barr Virus LMP1R15CA188941 · NCI · FLORIDA STATE UNIVERSITY · PI MECKES, DAVID G · 2015 to 2015
$414k
NCI NIH HHS R01 CA204621NCI NIH HHS R15 CA188941
6 · The paper itself

Abstract

Latent membrane protein 1 (LMP1) is an Epstein-Barr virus (EBV)-encoded oncoprotein that is packaged into small extracellular vesicles (EVs) called exosomes. Trafficking of LMP1 into multivesicular bodies (MVBs) alters the content and function of exosomes. LMP1-modified exosomes enhance the growth, migration, and invasion of malignant cells, demonstrating the capacity to manipulate the tumor microenvironment and enhance the progression of EBV-associated cancers. Despite the growing evidence surrounding the significance of LMP1-modified exosomes in cancer, very little is understood about the mechanisms that orchestrate LMP1 incorporation into these vesicles. Recently, LMP1 was shown to be copurified with CD63, a conserved tetraspanin protein enriched in late endosomal and lysosomal compartments. Here, we demonstrate the importance of CD63 presence for exosomal packaging of LMP1. Nanoparticle tracking analysis and gradient purification revealed an increase in extracellular vesicle secretion and exosomal proteins following LMP1 expression. Immunoisolation of CD63-positive exosomes exhibited accumulation of LMP1 in this vesicle population. Functionally, CRISPR/Cas9 knockout of CD63 resulted in a reduction of LMP1-induced particle secretion. Furthermore, LMP1 packaging was severely impaired in CD63 knockout cells, concomitant with a disruption in the perinuclear localization of LMP1. Importantly, LMP1 trafficking to lipid rafts and activation of NF-κB and PI3K/Akt pathways remained intact following CD63 knockout, while mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and noncanonical NF-κB activation were observed to be increased. These results suggest that CD63 is a critical player in LMP1 exosomal trafficking and LMP1-mediated enhancement of exosome production and may play further roles in limiting downstream LMP1 signaling.

Indexed as

Signal TransductionAnimalsExosomesHEK293 CellsHerpesvirus 4, HumanHumansMembrane MicrodomainsNF-kappa BProtein TransportRatsSecretory VesiclesTetraspanin 30Viral Matrix ProteinsCD63 protein, humanEBV-associated membrane antigen, Epstein-Barr virusNF-kappa BTetraspanin 30Viral Matrix Proteinscell signalingEpstein-Barr virusexosomesextracellular vesicleshuman herpesviruses

Identifiers

PMID27974566
PMCPMC5309960
OpenAlexW2569150814

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.