Evidence map›Paper›PMID 35066302›Full record

ArticleVirology2022

SARS-CoV-2 viroporin encoded by ORF3a triggers the NLRP3 inflammatory pathway.

Huanzhou Xu, Ibukun A Akinyemi, Siddhi A Chitre, Julia C Loeb, John A Lednicky, Michael T McIntosh, Sumita Bhaduri-McIntosh

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed
12.1field-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

130 citing papers in PubMed, 164 citations in OpenAlex.

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  12. Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  16. Molecular signaling in coinfection: howFrontiers in immunology · 2026
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  17. Article
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70 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 2 institutions in 1 country.

Huanzhou XuDivision of Infectious Disease, Department of Pediatrics, University of Florida, Gainesville, FL, USA.
Ibukun A AkinyemiChild Health Research Institute, Department of Pediatrics, University of Florida, Gainesville, FL, USA.
Siddhi A ChitreDivision of Infectious Disease, Department of Pediatrics, University of Florida, Gainesville, FL, USA.
Julia C LoebDepartment of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA; Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
John A LednickyDepartment of Environmental and Global Health, College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA; Emerging Pathogens Institute, University of Florida, Gainesville, FL, USA.
Michael T McIntoshChild Health Research Institute, Department of Pediatrics, University of Florida, Gainesville, FL, USA; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA.
Sumita Bhaduri-McIntoshDivision of Infectious Disease, Department of Pediatrics, University of Florida, Gainesville, FL, USA; Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL, USA. Electronic address: sbhadurimcintosh@ufl.edu.
University of Florida Health · USUniversity of Florida · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Heightened inflammatory response is a prominent feature of severe COVID-19 disease. We report that the SARS-CoV-2 ORF3a viroporin activates the NLRP3 inflammasome, the most promiscuous of known inflammasomes. Ectopically expressed ORF3a triggers IL-1β expression via NFκB, thus priming the inflammasome. ORF3a also activates the NLRP3 inflammasome but not NLRP1 or NLRC4, resulting in maturation of IL-1β and cleavage/activation of Gasdermin. Notably, ORF3a activates the NLRP3 inflammasome via both ASC-dependent and -independent modes. This inflammasome activation requires efflux of potassium ions and oligomerization between the kinase NEK7 and NLRP3. Importantly, infection of epithelial cells with SARS-CoV-2 similarly activates the NLRP3 inflammasome. With the NLRP3 inhibitor MCC950 and select FDA-approved oral drugs able to block ORF3a-mediated inflammasome activation, as well as key ORF3a amino acid residues needed for virus release and inflammasome activation conserved in the new variants of SARS-CoV-2 isolates across continents, ORF3a and NLRP3 present prime targets for intervention.

Indexed as

Signal TransductionAmino Acid SequenceAntiviral AgentsCell DeathCell LineCOVID-19Host-Pathogen InteractionsHumansInflammasomesModels, BiologicalNLR Family, Pyrin Domain-Containing 3 ProteinOpen Reading FramesPotassiumSARS-CoV-2Viroporin ProteinsAntiviral AgentsInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinPotassiumViroporin ProteinsAntiviralCOVID-19CytokineNLRP3 inflammasomeORF3aSARS-CoV-2Viroporin

Identifiers

PMID35066302
PMCPMC8762580
OpenAlexW4205454043

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.