SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator

Hysenaj, L.; Little, S.; Kulhanek, K. R.; Gbenedio, O.; Rodriguez, L.; Shen, A.; Lone, J.-C.; Lupin-Jimenez, L. C.; Bonser, L.; Serwas, N. K.; Bahl, K.; Mick, E.; Li, J. Z.; Ding, V.; Matsumoto, S.; Maishan, M. l.; Fragiadakis, G.; Jablons, D. M.; Langelier, C. R.; Matthay, M.; Ott, M.; Sil, A.; Krummel, M.; Combes, A. J.; Erle, D. M.; Kratz, J. R.; Roose, J. P.

doi:10.1101/2021.06.01.446640

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bioRxiv · 10.1101/2021.06.01.446640

SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator

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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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Hysenaj, L., Little, S., Kulhanek, K. R., Gbenedio, O., Rodriguez, L., Shen, A., Lone, J.-C., Lupin-Jimenez, L. C., Bonser, L., Serwas, N. K., Bahl, K., Mick, E., Li, J. Z., Ding, V., Matsumoto, S., Maishan, M. l., Fragiadakis, G., Jablons, D. M., Langelier, C. R., Matthay, M., Ott, M., Sil, A., Krummel, M., Combes, A. J., Erle, D. M., Kratz, J. R., Roose, J. P.. 2021-06-02. SARS-CoV-2 infection studies in lung organoids identify TSPAN8 as novel mediator. https://doi.org/10.1101/2021.06.01.446640

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