TY  - JOUR
AU  - Hysenaj, Lisiena
AU  - Little, Samantha
AU  - Kulhanek, Kayla
AU  - Magnen, Melia
AU  - Bahl, Kriti
AU  - Gbenedio, Oghenekevwe M
AU  - Prinz, Morgan
AU  - Rodriguez, Lauren
AU  - Andersen, Christopher
AU  - Rao, Arjun Arkal
AU  - Shen, Alan
AU  - Lone, Jean-Christophe
AU  - Lupin-Jimenez, Leonard C
AU  - Bonser, Luke R
AU  - Serwas, Nina K
AU  - Mick, Eran
AU  - Khalid, Mir M
AU  - Taha, Taha Y
AU  - Kumar, Renuka
AU  - Li, Jack Z
AU  - Ding, Vivianne W
AU  - Matsumoto, Shotaro
AU  - Maishan, Mazharul
AU  - Sreekumar, Bharath
AU  - Simoneau, Camille
AU  - Nazarenko, Irina
AU  - Tomlinson, Michael G
AU  - Khan, Khajida
AU  - von Gottberg, Anne
AU  - Sigal, Alex
AU  - Looney, Mark R
AU  - Fragiadakis, Gabriela K
AU  - Jablons, David M
AU  - Langelier, Charles R
AU  - Matthay, Michael
AU  - Krummel, Matthew
AU  - Erle, David J
AU  - Combes, Alexis J
AU  - Sil, Anita
AU  - Ott, Melanie
AU  - Kratz, Johannes R
AU  - Roose, Jeroen P
TI  - SARS-CoV-2 infection of airway organoids reveals conserved use of Tetraspanin-8 by Ancestral, Delta, and Omicron variants.
JO  - Stem cell reports
VL  - 18
IS  - 3
SN  - 2213-6711
CY  - [New York, NY]
PB  - Elsevier
M1  - DKFZ-2023-00565
SP  - 636 - 653
PY  - 2023
AB  - 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.
KW  - Humans
KW  - COVID-19
KW  - SARS-CoV-2
KW  - Influenza A Virus, H1N1 Subtype
KW  - Organoids
KW  - Tetraspanins: genetics
KW  - H1N1 (Other)
KW  - SARS-CoV-2 (Other)
KW  - TSPAN8 (Other)
KW  - airway organoids (Other)
KW  - cell composition (Other)
KW  - single cell RNAseq (Other)
KW  - spectral flow (Other)
KW  - therapeutics (Other)
KW  - variants (Other)
KW  - virus (Other)
KW  - Tetraspanins (NLM Chemicals)
KW  - TSPAN8 protein, human (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:36827975
C2  - pmc:PMC9948283
DO  - DOI:10.1016/j.stemcr.2023.01.011
UR  - https://inrepo02.dkfz.de/record/274363
ER  -