Journal Article

DKFZ-2023-00565

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.

Hysenaj, L. ; Little, S. ; Kulhanek, K. ; Magnen, M. ; Bahl, K. ; Gbenedio, O. M. ; Prinz, M. ; Rodriguez, L. ; Andersen, C. ; Rao, A. A. ; Shen, A. ; Lone, J.-C. ; Lupin-Jimenez, L. C. ; Bonser, L. R. ; Serwas, N. K. ; Mick, E. ; Khalid, M. M. ; Taha, T. Y. ; Kumar, R. ; Li, J. Z. ; Ding, V. W. ; Matsumoto, S. ; Maishan, M. ; Sreekumar, B. ; Simoneau, C. ; Nazarenko, I.DKFZ* ; Tomlinson, M. G. ; Khan, K. ; von Gottberg, A. ; Sigal, A. ; Looney, M. R. ; Fragiadakis, G. K. ; Jablons, D. M. ; Langelier, C. R. ; Matthay, M. ; Krummel, M. ; Erle, D. J. ; Combes, A. J. ; Sil, A. ; Ott, M. ; Kratz, J. R. ; Roose, J. P.

2023
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.stemcr.2023.01.011

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.

Keyword(s): Humans (MeSH) ; COVID-19 (MeSH) ; SARS-CoV-2 (MeSH) ; Influenza A Virus, H1N1 Subtype (MeSH) ; Organoids (MeSH) ; Tetraspanins: genetics (MeSH) ; H1N1 ; SARS-CoV-2 ; TSPAN8 ; airway organoids ; cell composition ; single cell RNAseq ; spectral flow ; therapeutics ; variants ; virus ; Tetraspanins ; TSPAN8 protein, human

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Contributing Institute(s):

1. DKTK FR zentral (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2023

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Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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