ArticleStem cell reports2023
SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.
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Article in Stem cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Advances in human respiratory organoid models for studying the pathogenesis and intervention strategies of COVID-19.Virologica Sinica · 2026Review
- O-GlcNAcylation of AMFR stabilizes TSPAN4 to regulate migrasome formation for viral release.Nature communications · 2026Article
- Development, propagation and characterization of human somatic cell-derived bronchial organoids as model system for airway diseases - A practical guide.Frontiers in allergy · 2026Article
- MERS-CoV and SARS-CoV-2 infection in diverse human lung organoid-derived cultures.Journal of virology · 2025Article
- Single-cell proteomics characterization of bone marrow hematopoiesis with distinct Ras pathway lesions.Blood advances · 2025Article
- Article
- Airway epithelial SARS-CoV-2 infectious and repair responses: relationships to age, sex, and post-COVID pulmonary syndromes.bioRxiv : the preprint server for biology · 2025Article
- Article
- NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids.Scientific reports · 2024Article
- Review
- Parents' Views on Autopsy, Organ Donation, and Research Donation After Neonatal Death.JAMA network open · 2023Article
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Authors and funding
42 authors at 9 institutions in 4 countries.
Lisiena HysenajDepartment of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Samantha LittleDepartment of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Kayla KulhanekDepartment of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Melia MagnenImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Kriti BahlDepartment of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Oghenekevwe M GbenedioDepartment of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Morgan PrinzDepartment of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
Lauren RodriguezDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA.
Christopher AndersenUCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA.
Arjun Arkal RaoUCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Alan ShenUCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
Jean-Christophe LoneSchool of Life Science, University of Essex, C04 3SQ Colchester, UK.
Leonard C Lupin-JimenezUCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA.
Luke R BonserLung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Nina K SerwasDepartment of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Eran MickDivision of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA; Division of Pulmonary and Critical Care, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Mir M KhalidGladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Taha Y TahaGladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Renuka KumarGladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jack Z LiDepartment of Surgery, Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA, USA.
Vivianne W DingDepartment of Surgery, Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA, USA.
Shotaro MatsumotoCardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA 94143, USA.
Mazharul MaishanCardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA 94143, USA.
Bharath SreekumarGladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Camille SimoneauGladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Irina NazarenkoInstitute for Infection Prevention and Hospital Epidemiology, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; German Cancer Consortium, Partner Site Freiburg and German Cancer Research Center, Heidelberg, Germany.
Michael G TomlinsonSchool of Biosciences, University of Birmingham, Birmingham, UK; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Midlands, UK.
Khajida KhanAfrica Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.
Anne von GottbergNational Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa; SAMRC Antibody Immunity Research Unit, University of the Witwatersrand, Johannesburg, South Africa.
Alex SigalAfrica Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa; Max Planck Institute for Infection Biology, Berlin, Germany; Centre for the AIDS Program of Research, Durban, South Africa.
Mark R LooneyImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Division of Pulmonary and Critical Care, San Francisco, San Francisco, CA, USA.
Gabriela K FragiadakisUCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, CA 94143, USA.
David M JablonsDivision of Pulmonary and Critical Care, San Francisco, San Francisco, CA, USA; Department of Surgery, Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA 94143, USA.
Charles R LangelierDivision of Infectious Diseases, University of California, San Francisco, San Francisco, CA, USA; Division of Pulmonary and Critical Care, San Francisco, San Francisco, CA, USA; Gladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
Michael MatthayDivision of Pulmonary and Critical Care, San Francisco, San Francisco, CA, USA; Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA 94143, USA.
Matthew KrummelDepartment of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
David J ErleUCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Division of Pulmonary and Critical Care, San Francisco, San Francisco, CA, USA.
Alexis J CombesUCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Anita SilDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Melanie OttGladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, CA 94143, USA; Quantitative Biosciences Institute COVID-19 Research Group, University of California, San Francisco, San Francisco, CA, USA.
Johannes R KratzImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Department of Surgery, Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA, USA.
Jeroen P RooseDepartment of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: jeroen.roose@ucsf.edu.
University of California, San Francisco · USGladstone Institutes · USPulmonary and Critical Care Associates · USAfrica Health Research Institute · ZAGerman Cancer Research Center · DEMax Planck Institute for Infection Biology · DESouth African Medical Research Council · ZAUniversity of Birmingham · GBUniversity of Essex · GB
Funding
Understanding Asthma EndotypesU19AI077439 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRESCOTT G WOODRUFF · 2008 to 2026
$41.1MUnderstand the metabolic fitness of naïve T cellsP01AI091580 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEROEN ROOSE · 2011 to 2026
$31.1MAirway epithelial cell gene regulation: new mechanisms and therapeutic strategiesR35HL145235 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ERLE, DAVID J · 2019 to 2025
$6.8MMicrobial Pathogenesis and Host DefenseT32AI060537 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Joanne N. Engel · 2004 to 2026
$6.5MRole of Factor Acetylation in the Regulation of HIV TranscriptionR37AI083139 · NIAID · J. DAVID GLADSTONE INSTITUTES · PI Melanie Maria Ott · 2019 to 2026
$5.5MImmunobiology of the normal and injured lungR35HL161241 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARK ROBERTS LOONEY · 2022 to 2026
$4.2MMechanisms and pathogenicity of SARS-CoV-2-induced neutrophil extracellular trapsR01AI160167 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LOONEY, MARK ROBERTS · 2021 to 2025
$3.1MIdentification of the HIV Reservoir in Lymph Nodes Using Single Cell RNA-SeqR01AI138546 · NIAID · KWAZULU-NATAL RESEARCH INSTITUTE TB-HIV · PI SIGAL, ALEXANDER · 2018 to 2022
$721kNHLBI NIH HHS R35 HL145235NHLBI NIH HHS R35 HL161241NIAID NIH HHS P01 AI091580NIAID NIH HHS R01 AI138546NIAID NIH HHS R01 AI160167NIAID NIH HHS R37 AI083139NIAID NIH HHS T32 AI060537NIAID NIH HHS U19 AI077439
Abstract
Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease severity. The mechanistic explaining variations related to airway epithelium are relatively understudied. Here, we biobanked airway organoids (AO) by preserving stem cell function. We optimized viral infection with H1N1/PR8 and comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable AO from 20 different subjects. We discovered Tetraspanin-8 (TSPAN8) as a facilitator of SARS-CoV-2 infection. TSPAN8 facilitates SARS-CoV-2 infection rates independently of ACE2-Spike interaction. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta and Omicron VOC displayed lower overall infection rates of AO but triggered changes in epithelial response. All variants shared highest tropism for ciliated and goblet cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.
Indexed as
COVID-19Influenza A Virus, H1N1 SubtypeHumansOrganoidsSARS-CoV-2TetraspaninsTetraspaninsTSPAN8 protein, humanairway organoidscell compositionH1N1SARS-CoV-2single cell RNAseqspectral flowtherapeuticsTSPAN8variantsvirus
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