SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator
- 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
- et al.
Published Web Location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183007/Abstract
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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