Evidence map›Paper›PMID 34214467›Full record

ArticleCell reports2021

Systematic analysis of SARS-CoV-2 infection of an ACE2-negative human airway cell.

Maritza Puray-Chavez, Kyle M LaPak, Travis P Schrank, Jennifer L Elliott, Dhaval P Bhatt, Megan J Agajanian, Ria Jasuja, Dana Q Lawson, Keanu Davis, Paul W Rothlauf and 21 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.

0numbers the graph read from it
0cells of the map it votes in
104citing papers in PubMed
8.5field-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

104 citing papers in PubMed, 149 citations in OpenAlex.

  1. Article
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  3. Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  4. Molecular mechanisms of SARS-CoV-2 entry: implications for biomedical strategies.Microbiology and molecular biology reviews : MMBR · 2025
    Review
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  11. Biomarker insights · 2025
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  14. Review
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  16. Review
  17. Review
  18. Article
  19. Article
  20. Article

44 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 4 institutions in 1 country.

Maritza Puray-ChavezDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Kyle M LaPakDepartment of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Travis P SchrankLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA; Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Jennifer L ElliottDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Dhaval P BhattDepartment of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Megan J AgajanianDepartment of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Ria JasujaDepartment of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Dana Q LawsonDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Keanu DavisDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Paul W RothlaufDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Program in Virology, Harvard Medical School, Boston, MA, USA.
Zhuoming LiuDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Heejoon JoUniversity of Tennessee Health Science Center for Cancer Research, Department of Medicine, Division of Hematology and Oncology, University of Tennessee, Memphis, TN, USA.
Nakyung LeeDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Kasyap TennetiDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Jenna E EschbachDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Christian Shema MugishaDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Emily M CousinsLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Erica W CloerLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
Hung R VuongDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Laura A VanBlarganDepartment of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA.
Adam L BaileyDepartment of Pathology & Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Pavlo GilchukVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
James E CroweVanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Michael S DiamondDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pathology & Immunology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO 63110, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, St. Louis, MO 63110, USA.
D Neil HayesUniversity of Tennessee Health Science Center for Cancer Research, Department of Medicine, Division of Hematology and Oncology, University of Tennessee, Memphis, TN, USA.
Sean P J WhelanDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Amjad HoraniDepartment of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Pediatrics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Steven L BrodyDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
Dennis GoldfarbDepartment of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Institute for Informatics, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA.
M Ben MajorDepartment of Cell Biology and Physiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA; Department of Otolaryngology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA. Electronic address: bmajor@wustl.edu.
Sebla B KutluayDepartment of Molecular Microbiology, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA. Electronic address: kutluay@wustl.edu.
Washington University in St. Louis · USUniversity of North Carolina at Chapel Hill · USUniversity of Tennessee Health Science Center · USVanderbilt University Medical Center · US

Funding

WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
TRAINING IN THE IMMUNOBIOLOGY AND MOLECULAR CELL BIOLOGY OF CANCERT32CA009547 · NCI · WASHINGTON UNIVERSITY · PI ROBERT DAVID SCHREIBER · 1986 to 2026
$12.1M
B-CELL EPITOPE DISCOVERY AND MECHANISMS OF ANTIBODY PROTECTION: Modification for SARS-CoV2 Research75N93019C00074 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI CROWE, JAMES E · 2019 to 2024
$10.2M
TRAINING IN RESPIRATORY AND ENVIRONMENTAL MEDICINET32HL007106 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BOUCHER, RICHARD CHARLES, DOERSCHUK, CLAIRE M · 1985 to 2021
$7.3M
Human antibody-based countermeasures against the Wuhan Coronavirus SARS-CoV-2R01AI157155 · NIAID · WASHINGTON UNIVERSITY · PI BARIC, RALPH S, CROWE, JAMES E · 2020 to 2024
$6.0M
RNA Processing in Non-Segmented Minus-Strand RNA VirusesR37AI059371 · NIAID · WASHINGTON UNIVERSITY · PI WHELAN, SEAN PJ · 2015 to 2024
$5.4M
RNA Processing in Non-Segmented Minus-Strand RNA VirusesR01AI059371 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WHELAN, SEAN PJ · 2005 to 2015
$3.9M
The Role of Protein Kinases in NRF2-driven Lung Squamous Cell CarcinomaR01CA216051 · NCI · WASHINGTON UNIVERSITY · PI MAJOR, MICHAEL BENJAMIN, WEISSMAN, BERNARD E. · 2018 to 2022
$2.5M
Mechanisms Determining Dysregulation of the NRF2 Oxidative Stress Response in Head and Neck Squamous Cell CarcinomaK08DE029241 · NIDCR · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SCHRANK, TRAVIS P. · 2020 to 2024
$870k
The Role of Dynein Motor Mutations in Motile Cilia DiseaseK08HL150223 · NHLBI · WASHINGTON UNIVERSITY · PI HORANI, AMJAD · 2020 to 2024
$797k
NCATS NIH HHS UL1 TR002345NCI NIH HHS R01 CA216051NCI NIH HHS T32 CA009547NHLBI NIH HHS K08 HL150223NHLBI NIH HHS T32 HL007106NIAID NIH HHS 75N93019C00074NIAID NIH HHS R01 AI059371NIAID NIH HHS R01 AI157155NIAID NIH HHS R37 AI059371NIDCR NIH HHS K08 DE029241
6 · The paper itself

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) variants govern transmissibility, responsiveness to vaccination, and disease severity. In a screen for new models of SARS-CoV-2 infection, we identify human H522 lung adenocarcinoma cells as naturally permissive to SARS-CoV-2 infection despite complete absence of angiotensin-converting enzyme 2 (ACE2) expression. Remarkably, H522 infection requires the E484D S variant; viruses expressing wild-type S are not infectious. Anti-S monoclonal antibodies differentially neutralize SARS-CoV-2 E484D S in H522 cells as compared to ACE2-expressing cells. Sera from vaccinated individuals block this alternative entry mechanism, whereas convalescent sera are less effective. Although the H522 receptor remains unknown, depletion of surface heparan sulfates block H522 infection. Temporally resolved transcriptomic and proteomic profiling reveal alterations in cell cycle and the antiviral host cell response, including MDA5-dependent activation of type I interferon signaling. These findings establish an alternative SARS-CoV-2 host cell receptor for the E484D SARS-CoV-2 variant, which may impact tropism of SARS-CoV-2 and consequently human disease pathogenesis.

Indexed as

Receptors, VirusAmino Acid SubstitutionAngiotensin-Converting Enzyme 2AnimalsAntibodies, MonoclonalAntibodies, ViralCell CycleCell Line, TumorChlorocebus aethiopsCOVID-19Gene Expression ProfilingHeparan SulfateHumansInterferon-Induced Helicase, IFIH1Interferon Type IModels, BiologicalACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, MonoclonalAntibodies, ViralHeparan SulfateIFIH1 protein, humanInterferon-Induced Helicase, IFIH1Interferon Type IReceptors, VirusSerine EndopeptidasesSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2TMPRSS2 protein, humanACE2-independentclathrin-mediated endocytosisCOVID-19heparan sulfateproteomicsRIG-I-like receptorsSARS-CoV-2spike variantstype I interferonvirus-host interactions

Identifiers

PMID34214467
PMCPMC8220945
OpenAlexW3175341024

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.