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

H1N1 SARS-CoV-2 TSPAN8 airway organoids cell composition single cell RNAseq spectral flow therapeutics variants virus

Journal

Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300

Informations de publication

Date de publication:
14 03 2023
Historique:
received: 12 12 2022
revised: 23 01 2023
accepted: 24 01 2023
pubmed: 25 2 2023
medline: 21 3 2023
entrez: 24 2 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36827975
pii: S2213-6711(23)00014-0
doi: 10.1016/j.stemcr.2023.01.011
pmc: PMC9948283
pii:
doi:

Substances chimiques

Tetraspanins 0
TSPAN8 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

636-653

Subventions

Organisme : NIAID NIH HHS
ID : T32 AI060537
Pays : United States
Organisme : NIAID NIH HHS
ID : R37 AI083139
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI091580
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL145235
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI138546
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI077439
Pays : United States

Informations de copyright

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

Déclaration de conflit d'intérêts

Conflict of interests The authors have no competing interests. A patent “INHIBITORS OF SARS-COV-2 INFECTION AND OTHER CORONA VIRUS INFECTIONS” SF-2021-201-2-PCT-0 has been filed.

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Auteurs

Lisiena Hysenaj (L)

Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Samantha Little (S)

Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Kayla Kulhanek (K)

Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Melia Magnen (M)

ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.

Kriti Bahl (K)

Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Oghenekevwe M Gbenedio (OM)

Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Morgan Prinz (M)

Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA.

Lauren Rodriguez (L)

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.

Christopher Andersen (C)

UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA.

Arjun Arkal Rao (AA)

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.

Alan Shen (A)

UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.

Jean-Christophe Lone (JC)

School of Life Science, University of Essex, C04 3SQ Colchester, UK.

Leonard C Lupin-Jimenez (LC)

UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; ImmunoX Initiative, University of California, San Francisco, San Francisco, CA, USA.

Luke R Bonser (LR)

Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Nina K Serwas (NK)

Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.

Eran Mick (E)

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.

Mir M Khalid (MM)

Gladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Taha Y Taha (TY)

Gladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Renuka Kumar (R)

Gladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Jack Z Li (JZ)

Department of Surgery, Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA, USA.

Vivianne W Ding (VW)

Department of Surgery, Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, CA, USA.

Shotaro Matsumoto (S)

Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA 94143, USA.

Mazharul Maishan (M)

Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, CA 94143, USA.

Bharath Sreekumar (B)

Gladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Camille Simoneau (C)

Gladstone Institute of Virology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.

Irina Nazarenko (I)

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.

Michael G Tomlinson (MG)

School of Biosciences, University of Birmingham, Birmingham, UK; Centre of Membrane Proteins and Receptors, Universities of Birmingham and Nottingham, Midlands, UK.

Khajida Khan (K)

Africa Health Research Institute, Durban, South Africa; School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

Anne von Gottberg (A)

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.

Alex Sigal (A)

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.

Mark R Looney (MR)

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.

Gabriela K Fragiadakis (GK)

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.

David M Jablons (DM)

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.

Charles R Langelier (CR)

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.

Michael Matthay (M)

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.

Matthew Krummel (M)

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.

David J Erle (DJ)

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.

Alexis J Combes (AJ)

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.

Anita Sil (A)

Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.

Melanie Ott (M)

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.

Johannes R Kratz (JR)

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.

Jeroen P Roose (JP)

Department of Anatomy, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. Electronic address: jeroen.roose@ucsf.edu.

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