Evidence map›Paper›PMID 28848230›Full record

ArticleNature microbiology2017

Specific inhibition of NLRP3 in chikungunya disease reveals a role for inflammasomes in alphavirus-induced inflammation.

Weiqiang Chen, Suan-Sin Foo, Ali Zaid, Terk-Shin Teng, Lara J Herrero, Stefan Wolf, Kothila Tharmarajah, Luan D Vu, Caryn van Vreden, Adam Taylor and 14 more

Open access · greenAbstract read
PubMed Publisher
In one paragraph

Article in Nature microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
11.4field-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

60 citing papers in PubMed, 91 citations in OpenAlex.

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  2. The oxidative stress paradigm in arbovirus infections: mechanisms and therapeutic insights.Redox report : communications in free radical research · 2026
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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

24 authors at 10 institutions in 6 countries.

Weiqiang ChenEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Suan-Sin FooEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Ali ZaidEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Terk-Shin TengSingapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, 138632, Singapore.
Lara J HerreroEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Stefan WolfEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Kothila TharmarajahEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Luan D VuDiscipline of Pathology, Bosch Institute, School of Medical Sciences, Sydney Medical School, Charles Perkins Centre, University of Sydney, Camperdown, NSW, 2006, Australia.
Caryn van VredenDiscipline of Pathology, Bosch Institute, School of Medical Sciences, Sydney Medical School, Charles Perkins Centre, University of Sydney, Camperdown, NSW, 2006, Australia.
Adam TaylorEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Joseph R FreitasEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia.
Rachel W LiThe Medical School, The Australian National University, Acton, ACT, 2601, Australia.
Trent M WoodruffSchool of Biomedical Science, The University of Queensland, Australia, St Lucia, QLD, 4072, Australia.
Richard GordonSchool of Biomedical Science, The University of Queensland, Australia, St Lucia, QLD, 4072, Australia.
David M OjciusDepartment of Biomedical Sciences, University of the Pacific, San Francisco, CA, 94103, USA.
Helder I NakayaDepartment of Pathophysiology and Toxicology, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, CEP 05508-000, Brazil.ORCID http://orcid.org/0000-0001-5297-9108
Thirumala-Devi KannegantiDepartment of Immunology, St Jude's Children's Hospital, Memphis, TN, 38105, USA.
Luke A J O'NeillTrinity Biomedical Sciences Institute, Trinity College Dublin, The University of Dublin, College Green, Dublin, 2, Ireland.
Avril A B RobertsonInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.
Nicholas J KingDiscipline of Pathology, Bosch Institute, School of Medical Sciences, Sydney Medical School, Charles Perkins Centre, University of Sydney, Camperdown, NSW, 2006, Australia.
Andreas SuhrbierInflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Matthew A CooperInstitute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, 4072, Australia.
Lisa F P NgSingapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, 138632, Singapore.
Suresh MahalingamEmerging Viruses and Inflammation Research Group, Institute for Glycomics, Griffith University, Gold Coast, QLD, 4222, Australia. s.mahalingam@griffith.edu.au.ORCID http://orcid.org/0000-0003-3141-8410
Griffith University · AUThe University of Queensland · AUThe University of Sydney · AUAgency for Science, Technology and Research · SGAustralian National University · AUQIMR Berghofer Medical Research Institute · AUSt. Jude Children's Research Hospital · USTrinity College Dublin · IEUniversidade de São Paulo · BRUniversity of the Pacific · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mosquito-borne viruses can cause severe inflammatory diseases and there are limited therapeutic solutions targeted specifically at virus-induced inflammation. Chikungunya virus (CHIKV), a re-emerging alphavirus responsible for several outbreaks worldwide in the past decade, causes debilitating joint inflammation and severe pain. Here, we show that CHIKV infection activates the NLRP3 inflammasome in humans and mice. Peripheral blood mononuclear cells isolated from CHIKV-infected patients showed elevated NLRP3, caspase-1 and interleukin-18 messenger RNA expression and, using a mouse model of CHIKV infection, we found that high NLRP3 expression was associated with peak inflammatory symptoms. Inhibition of NLRP3 activation using the small-molecule inhibitor MCC950 resulted in reduced CHIKV-induced inflammation and abrogated osteoclastogenic bone loss and myositis, but did not affect in vivo viral replication. Mice treated with MCC950 displayed lower expression levels of the cytokines interleukin-6, chemokine ligand 2 and tumour necrosis factor in joint tissue. Interestingly, MCC950 treatment abrogated disease signs in mice infected with a related arthritogenic alphavirus, Ross River virus, but not in mice infected with West Nile virus-a flavivirus. Here, using mouse models of alphavirus-induced musculoskeletal disease, we demonstrate that NLRP3 inhibition in vivo can reduce inflammatory pathology and that further development of therapeutic solutions targeting inflammasome function could help treat arboviral diseases.

Indexed as

InflammationAlphavirusAnimalsCaspase 1ChemokinesChikungunya FeverChikungunya virusChlorocebus aethiopsCytokinesDisease Models, AnimalFemaleHumansInflammasomesInterleukin-18Interleukin-6Leukocytes, MononuclearCaspase 1ChemokinesCytokinesInflammasomesInterleukin-18Interleukin-6NLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseRNA, Messenger

Identifiers

PMID28848230
OpenAlexW2747702378

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.