Evidence map›Paper›PMID 28245863›Full record

ArticleArthritis research & therapy2017

Epstein-Barr virus lytic infection promotes activation of Toll-like receptor 8 innate immune response in systemic sclerosis monocytes.

Antonella Farina, Giovanna Peruzzi, Valentina Lacconi, Stefania Lenna, Silvia Quarta, Edoardo Rosato, Anna Rita Vestri, Michael York, David H Dreyfus, Alberto Faggioni and 3 more

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
6.9field-weighted citation impact, top 2% 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

40 citing papers in PubMed, 79 citations in OpenAlex.

  1. Review
  2. GATA2 Mediates Macrophage Proliferation During Atherosclerosis.Journal of the American Heart Association · 2025
    Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Serum TLR2 and TLR9 in Prostate Cancer Patients in Relation to EBV Status.International journal of molecular sciences · 2024
    Article
  8. Article
  9. Review
  10. Review
  11. Article
  12. Review
  13. Current Concepts on the Pathogenesis of Systemic Sclerosis.Clinical reviews in allergy & immunology · 2023
    Review
  14. Article
  15. Review
  16. Review
  17. Article
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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

13 authors at 4 institutions in 2 countries.

Antonella FarinaRheumatology, Boston University School of Medicine, Arthritis Center, 72 E. Concord Street, E-5, Boston, MA, 02118, USA.
Giovanna PeruzziIstituto Italiano di Tecnologia, CLNS@Sapienza, Rome, Italy.
Valentina LacconiRheumatology, Boston University School of Medicine, Arthritis Center, 72 E. Concord Street, E-5, Boston, MA, 02118, USA.
Stefania LennaRheumatology, Boston University School of Medicine, Arthritis Center, 72 E. Concord Street, E-5, Boston, MA, 02118, USA.
Silvia QuartaDepartment of Clinical Medicine, Sapienza University, Rome, Italy.
Edoardo RosatoDepartment of Clinical Medicine, Sapienza University, Rome, Italy.
Anna Rita VestriDepartment of Public Health, Sapienza University, Rome, Italy.
Michael YorkRheumatology, Boston University School of Medicine, Arthritis Center, 72 E. Concord Street, E-5, Boston, MA, 02118, USA.
David H DreyfusDepartment of Pediatrics, Yale, New Haven, CT, USA.
Alberto FaggioniDepartment of Experimental Medicine, Sapienza University, Rome, Italy.
Stefania MorroneDepartment of Experimental Medicine, Sapienza University, Rome, Italy.
Maria TrojanowskaRheumatology, Boston University School of Medicine, Arthritis Center, 72 E. Concord Street, E-5, Boston, MA, 02118, USA.
G Alessandra FarinaRheumatology, Boston University School of Medicine, Arthritis Center, 72 E. Concord Street, E-5, Boston, MA, 02118, USA. farina@bu.edu.ORCID 0000-0002-3948-6920
Boston University · USSapienza University of Rome · ITItalian Institute of Technology · ITYale University · US

Funding

Project-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3M
The molecular mechanisms of fibrosisR01AR042334 · NIAMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI TROJANOWSKA, MARIA · 1994 to 2018
$5.2M
Interplay between Type I IFN and TGF-beta signaling in systemic sclerosisR03AR062721 · NIAMS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI FARINA, GIUSEPPINA ALESSANDRA · 2012 to 2014
$240k
NCATS NIH HHS UL1 TR001430NIAMS NIH HHS R01 AR042334NIAMS NIH HHS R03 AR062721
6 · The paper itself

Abstract

backgroundMonocytes/macrophages are activated in several autoimmune diseases, including systemic sclerosis (scleroderma; SSc), with increased expression of interferon (IFN)-regulatory genes and inflammatory cytokines, suggesting dysregulation of the innate immune response in autoimmunity. In this study, we investigated whether the lytic form of Epstein-Barr virus (EBV) infection (infectious EBV) is present in scleroderma monocytes and contributes to their activation in SSc.

methodsMonocytes were isolated from peripheral blood mononuclear cells (PBMCs) depleted of the CD19+ cell fraction, using CD14/CD16 negative-depletion. Circulating monocytes from SSc and healthy donors (HDs) were infected with EBV. Gene expression of innate immune mediators were evaluated in EBV-infected monocytes from SSc and HDs. Involvement of Toll-like receptor (TLR)8 in viral-mediated TLR8 response was investigated by comparing the TLR8 expression induced by infectious EBV to the expression stimulated by CL075/TLR8/agonist-ligand in the presence of TLR8 inhibitor in THP-1 cells.

resultsInfectious EBV strongly induced TLR8 expression in infected SSc and HD monocytes in vitro. Markers of activated monocytes, such as IFN-regulated genes and chemokines, were upregulated in SSc- and HD-EBV-infected monocytes. Inhibiting TLR8 expression reduced virally induced TLR8 in THP-1 infected cells, demonstrating that innate immune activation by infectious EBV is partially dependent on TLR8. Viral mRNA and proteins were detected in freshly isolated SSc monocytes. Microarray analysis substantiated the evidence of an increased IFN signature and altered level of TLR8 expression in SSc monocytes carrying infectious EBV compared to HD monocytes.

conclusionThis study provides the first evidence of infectious EBV in monocytes from patients with SSc and links EBV to the activation of TLR8 and IFN innate immune response in freshly isolated SSc monocytes. This study provides the first evidence of EBV replication activating the TLR8 molecular pathway in primary monocytes. Immunogenicity of infectious EBV suggests a novel mechanism mediating monocyte inflammation in SSc, by which EBV triggers the innate immune response in infected cells.

Indexed as

AdultAgedBlotting, WesternCell Line, TumorCells, CulturedEpstein-Barr Virus InfectionsFemaleGene ExpressionGene Expression ProfilingHerpesvirus 4, HumanHost-Pathogen InteractionsHumansImmunity, InnateMaleMiddle AgedMonocytesCL 075QuinolinesThiazolesTLR8 protein, humanToll-Like Receptor 8EBV reactivationIFN inducible genesInnate immune responseMonocytesSystemic sclerosisToll-like receptor 8

Identifiers

PMID28245863
PMCPMC5331713
OpenAlexW2591925184

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.