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

Lisiena Hysenaj; Samantha Little; Kayla Kulhanek; Oghenekevwe M Gbenedio; Lauren Rodriguez; Alan Shen; Jean-Christophe Lone; Leonard C Lupin-Jimenez; Luke R Bonser; Nina K Serwas; Kriti Bahl; Eran Mick; Jack Z Li; Vivianne W Ding; Shotaro Matsumoto; Mazharul Maishan; Camille Simoneau; Gabriela Fragiadakis; David M Jablons; Charles R Langelier; Michael Matthay; Melanie Ott; Matthew Krummel; Alexis J Combes; Anita Sil; David J Erle; Johannes R Kratz; Jeroen P Roose

doi:10.1101/2021.06.01.446640

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

bioRxiv [Preprint]. 2021 Jun 2:2021.06.01.446640. doi: 10.1101/2021.06.01.446640.

Authors

Lisiena Hysenaj¹, Samantha Little¹, Kayla Kulhanek¹, Oghenekevwe M Gbenedio¹, Lauren Rodriguez^{2

3}, Alan Shen³, Jean-Christophe Lone⁴, Leonard C Lupin-Jimenez³, Luke R Bonser⁵, Nina K Serwas⁶, Kriti Bahl¹, Eran Mick⁷, Jack Z Li⁸, Vivianne W Ding⁸, Shotaro Matsumoto⁹, Mazharul Maishan⁹, Camille Simoneau¹⁰, Gabriela Fragiadakis³, David M Jablons⁸, Charles R Langelier^{7

11}, Michael Matthay⁹, Melanie Ott¹⁰, Matthew Krummel⁶, Alexis J Combes³, Anita Sil², David J Erle^{3

5}, Johannes R Kratz⁸, Jeroen P Roose¹

Affiliations

¹ Department of Anatomy, University of California, San Francisco, San Francisco, California 94143, USA.
² Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California 94143, USA.
³ UCSF CoLabs, University of California San Francisco, San Francisco, California 94143, USA.
⁴ School of Life Science, University of Essex, Wivenhoe Park,Colchester C04 3SQ, United Kingdom.
⁵ Lung Biology Center, Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
⁶ Department of Pathology, University of California, San Francisco, San Francisco, California 94143, USA.
⁷ Division of Infectious Diseases, University of California, San Francisco, San Francisco, California 94143, USA and Department of Surgery, Division of Cardiothoracic Surgery, University of California, San Francisco, San Francisco, California 94143, USA.
⁸ Cardiovascular Research Institute, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, California 94143, USA.
⁹ Gladstone Institute of Virology, Department of Medicine, University of California San Francisco, California 94143, USA.
¹⁰ Department of Medicine, Division of Rheumatology, University of California, San Francisco, San Francisco, California 94143, USA.
¹¹ Chan Zuckerberg Biohub, San Francisco, California 94158, USA.

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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Abstract

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