Evidence map›Paper›PMID 34188167›Full record

ArticleScientific reports2021

Activation of NF-κB and induction of proinflammatory cytokine expressions mediated by ORF7a protein of SARS-CoV-2.

Chia-Ming Su, Leyi Wang, Dongwan Yoo

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 3 pooled it
14.0field-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

132 citing papers in PubMed, 3 syntheses or guidelines pooled it, 202 citations in OpenAlex.

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  13. SARS-CoV-2 uptake and inflammatory response in senescent endothelial cells are regulated by the BSG/VEGFR2 pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025
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72 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

3 authors at 1 institution in 1 country.

Chia-Ming SuDepartment of Pathobiology, University of Illinois at Urbana-Champaign, 2001 Lincoln Ave, Urbana, IL, 61802, USA.ORCID 0000-0001-9317-5886
Leyi WangDepartment of Veterinary Diagnostic Laboratory and Department of Veterinary Clinical Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID 0000-0001-5813-9505
Dongwan YooDepartment of Pathobiology, University of Illinois at Urbana-Champaign, 2001 Lincoln Ave, Urbana, IL, 61802, USA. dyoo@illinois.edu.
University of Illinois Urbana-Champaign · US

Funding

United States Department of Agriculture | National Institute of Food and Agriculture (NIFA) 2018-67015-28287
6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19) that emerged in human populations recently. Severely ill COVID-19 patients exhibit the elevation of proinflammatory cytokines, and such an unbalanced production of proinflammatory cytokines is linked to acute respiratory distress syndrome with high mortality in COVID-19 patients. Our study provides evidence that the ORF3a, M, ORF7a, and N proteins of SARS-CoV-2 were NF-κB activators. The viral sequence from infected zoo lions belonged to clade V, and a single mutation of G251V is found for ORF3a gene compared to all other clades. No significant functional difference was found for clade V ORF3a, indicating the NF-κB activation is conserved among COVID-19 variants. Of the four viral proteins, the ORF7a protein induced the NF-κB dictated proinflammatory cytokines including IL-1α, IL-1β, IL-6, IL-8, IL-10, TNF-α, and IFNβ. The ORF7a protein also induced IL-3, IL-4, IL-7, IL-23. Of 15 different chemokines examined in the study, CCL11, CCL17, CCL19, CCL20, CCL21, CCL22, CCL25, CCL26, CCL27, and CXCL9 were significantly upregulated by ORF7. These cytokines and chemokines were frequently elevated in severely ill COVID-19 patients. Our data provide an insight into how SARS-CoV-2 modulates NF-κB signaling and inflammatory cytokine expressions. The ORF7a protein may be a desirable target for strategic developments to minimize uncontrolled inflammation in COVID-19 patients.

Indexed as

Amino Acid SequenceChemokinesCoronavirus M ProteinsCOVID-19CytokinesHeLa CellsHumansNF-kappa BPoint MutationSARS-CoV-2Sequence AlignmentSeverity of Illness IndexUp-RegulationViral Matrix ProteinsViral ProteinsViroporin ProteinsChemokinesCoronavirus M ProteinsCytokinesmembrane protein, SARS-CoV-2NF-kappa BORF3a protein, SARS-CoV-2ORF7a protein, SARS-CoV-2Viral Matrix ProteinsViral ProteinsViroporin Proteins

Identifiers

PMID34188167
PMCPMC8242070
OpenAlexW3174247674

What OpenQuestion holds

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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.