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SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.

Authors
  • Hysenaj, Lisiena1
  • Little, Samantha1
  • Kulhanek, Kayla1
  • Magnen, Melia2
  • Bahl, Kriti1
  • Gbenedio, Oghenekevwe M1
  • Prinz, Morgan1
  • Rodriguez, Lauren3
  • Andersen, Christopher4
  • Rao, Arjun Arkal5
  • Shen, Alan6
  • Lone, Jean-Christophe7
  • Lupin-Jimenez, Leonard C4
  • Bonser, Luke R8
  • Serwas, Nina K9
  • Mick, Eran10
  • Khalid, Mir M11
  • Taha, Taha Y11
  • Kumar, Renuka11
  • Li, Jack Z12
  • And 22 more
  • 1 Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.
  • 2 ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 3 Department 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.
  • 4 UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA.
  • 5 UCSF 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.
  • 6 UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 7 School of Life Science, University of Essex, C04 3SQ Colchester, UK.
  • 8 Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • 9 Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 10 Division 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.
  • 11 Gladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • 12 Department of Surgery, Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA, USA.
  • 13 Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 14 Institute 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. , (Germany)
  • 15 School of Biosciences, University of Birmingham, Birmingham, UK; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Midlands, UK.
  • 16 Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa. , (South Africa)
  • 17 National 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. , (South Africa)
  • 18 Africa 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. , (Germany)
  • 19 ImmunoX 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.
  • 20 UCSF 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.
  • 21 Division 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.
  • 22 Division 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.
  • 23 Division 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.
  • 24 Department 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.
  • 25 UCSF 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.
  • 26 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • 27 Gladstone 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.
  • 28 ImmunoX 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.
  • 29 Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: [email protected].
Type
Published Article
Journal
Stem Cell Reports
Publisher
Elsevier
Publication Date
Mar 14, 2023
Volume
18
Issue
3
Pages
636–653
Identifiers
DOI: 10.1016/j.stemcr.2023.01.011
PMID: 36827975
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

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