Author: Hysenaj, Lisiena; Little, Samantha; Kulhanek, Kayla; Gbenedio, Oghenekevwe M.; Rodriguez, Lauren; Shen, Alan; Lone, Jean-Christophe; Lupin-Jimenez, Leonard C.; Bonser, Luke R.; Serwas, Nina K.; Bahl, Kriti; Mick, Eran; Li, Jack Z.; Ding, Vivianne W.; Matsumoto, Shotaro; Maishan, Mazharul; Simoneau, Camille; Fragiadakis, Gabriela; Jablons, David M.; Langelier, Charles R.; Matthay, Michael; Ott, Melanie; Krummel, Matthew; Combes, Alexis J.; Sil, Anita; Erle, David J.; Kratz, Johannes R.; Roose, Jeroen P.
Title: SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator Cord-id: i1ysg4l2 Document date: 2021_6_2
ID: i1ysg4l2
Snippet: SARS coronavirus-2 (SARS-CoV-2) is causing a global pandemic with large variation in COVID-19 disease spectrum. SARS-CoV-2 infection requires host receptor ACE2 on lung epithelium, but epithelial underpinnings of variation are largely unknown. We capitalized on comprehensive organoid assays to report remarkable variation in SARS-CoV-2 infection rates of lung organoids from different subjects. Tropism is highest for TUBA− and MUC5AC-positive organoid cells, but levels of TUBA−, MUC5A−, or A
Document: SARS coronavirus-2 (SARS-CoV-2) is causing a global pandemic with large variation in COVID-19 disease spectrum. SARS-CoV-2 infection requires host receptor ACE2 on lung epithelium, but epithelial underpinnings of variation are largely unknown. We capitalized on comprehensive organoid assays to report remarkable variation in SARS-CoV-2 infection rates of lung organoids from different subjects. Tropism is highest for TUBA− and MUC5AC-positive organoid cells, but levels of TUBA−, MUC5A−, or ACE2− positive cells do not predict infection rate. We identify surface molecule Tetraspanin 8 (TSPAN8) as novel mediator of SARS-CoV-2 infection, which is not downregulated by this specific virus. TSPAN8 levels, prior to infection, strongly correlate with infection rate and TSPAN8-blocking antibodies diminish SARS-CoV-2 infection. We propose TSPAN8 as novel functional biomarker and potential therapeutic target for COVID-19.
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