Evidence map›Paper›PMID 34205098›Full record

ArticleViruses2021

The Pro-Inflammatory Chemokines CXCL9, CXCL10 and CXCL11 Are Upregulated Following SARS-CoV-2 Infection in an AKT-Dependent Manner.

Victoria Callahan, Seth Hawks, Matthew A Crawford, Caitlin W Lehman, Holly A Morrison, Hannah M Ivester, Ivan Akhrymuk, Niloufar Boghdeh, Rafaela Flor, Carla V Finkielstein and 5 more

Open access · goldAbstract read
In one paragraph

Article in Viruses, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
83citing papers in PubMed, 1 pooled it
7.7field-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

83 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.

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23 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

15 authors at 5 institutions in 1 country.

Victoria CallahanNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.
Seth HawksDepartment of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
Matthew A CrawfordDivision of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.ORCID 0000-0003-0404-0061
Caitlin W LehmanDepartment of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.ORCID 0000-0002-8012-5377
Holly A MorrisonDepartment of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.ORCID 0000-0001-7358-7728
Hannah M IvesterGraduate Program in Translational Biology, Medicine and Health, Virginia Polytechnic Institute and State University, Roanoke, VA 24061, USA.
Ivan AkhrymukDepartment of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
Niloufar BoghdehNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.
Rafaela FlorNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.
Carla V FinkielsteinIntegrated Cellular Responses Laboratory, Department of Biological Sciences and Center for Drug Discovery, Fralin Biomedical Research Institute, Virginia Polytechnic Institute and State University, Roanoke, VA 24016, USA.ORCID 0000-0002-8417-4643
Irving Coy AllenDepartment of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
James Weger-LucarelliDepartment of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
Nisha DuggalDepartment of Biomedical Science and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Blacksburg, VA 24060, USA.
Molly A HughesDivision of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
Kylene Kehn-HallNational Center for Biodefense and Infectious Diseases, School of Systems Biology, George Mason University, Manassas, VA 20110, USA.ORCID 0000-0001-8036-7213
Virginia–Maryland College of Veterinary Medicine · USGeorge Mason University · USUniversity of Virginia · USBiomedical Research Institute · USVirginia Tech · US

Funding

A unique strategy for reshaping the antibiotics model: chemokine-inspired therapeutics for targeting the host and pathogen to counter infections caused by multidrug-resistant bacteriaR01AI150941 · NIAID · UNIVERSITY OF VIRGINIA · PI HUGHES, MOLLY A · 2020 to 2024
$3.1M
NIAID NIH HHS R01 AI150941NIH HHS R01 AI150941
6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible RNA virus that is the causative agent of the Coronavirus disease 2019 (COVID-19) pandemic. Patients with severe COVID-19 may develop acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) and require mechanical ventilation. Key features of SARS-CoV-2 induced pulmonary complications include an overexpression of pro-inflammatory chemokines and cytokines that contribute to a 'cytokine storm.' In the current study an inflammatory state in Calu-3 human lung epithelial cells was characterized in which significantly elevated transcripts of the immunostimulatory chemokines CXCL9, CXCL10, and CXCL11 were present. Additionally, an increase in gene expression of the cytokines IL-6, TNFα, and IFN-γ was observed. The transcription of CXCL9, CXCL10, IL-6, and IFN-γ was also induced in the lungs of human transgenic angiotensin converting enzyme 2 (ACE2) mice infected with SARS-CoV-2. To elucidate cell signaling pathways responsible for chemokine upregulation in SARS-CoV-2 infected cells, small molecule inhibitors targeting key signaling kinases were used. The induction of CXCL9, CXCL10, and CXCL11 gene expression in response to SARS-CoV-2 infection was markedly reduced by treatment with the AKT inhibitor GSK690693. Samples from COVID-19 positive individuals also displayed marked increases in CXCL9, CXCL10, and CXCL11 transcripts as well as transcripts in the AKT pathway. The current study elucidates potential pathway specific targets for reducing the induction of chemokines that may be contributing to SARS-CoV-2 pathogenesis via hyperinflammation.

Indexed as

Up-RegulationAngiotensin-Converting Enzyme 2AnimalsCell LineChemokine CXCL10Chemokine CXCL11Chemokine CXCL9COVID-19Cytokine Release SyndromeEpithelial CellsFemaleHumansInflammationLungMiceMice, TransgenicACE2 protein, humanAKT1 protein, humanAngiotensin-Converting Enzyme 2Chemokine CXCL10Chemokine CXCL11Chemokine CXCL9CXCL10 protein, humanCxcl10 protein, mouseCXCL11 protein, humanCxcl11 protein, mouseCXCL9 protein, humanCxcl9 protein, mouseProto-Oncogene Proteins c-aktALIARDSbetacoronavirusCalu-3CXCL10cytokine stormhACE2 miceSARS-CoV-2

Identifiers

PMID34205098
PMCPMC8226769
OpenAlexW3171016257

What OpenQuestion holds

Textmetadata
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.