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

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.
Competing Interest Statement
The authors have declared no competing interest.
Subject Area
- Biochemistry (13867)
- Bioengineering (10569)
- Bioinformatics (33583)
- Biophysics (17309)
- Cancer Biology (14374)
- Cell Biology (20354)
- Clinical Trials (138)
- Developmental Biology (10972)
- Ecology (16203)
- Epidemiology (2067)
- Evolutionary Biology (20510)
- Genetics (13510)
- Genomics (18802)
- Immunology (13932)
- Microbiology (32476)
- Molecular Biology (13523)
- Neuroscience (70800)
- Paleontology (532)
- Pathology (2222)
- Pharmacology and Toxicology (3778)
- Physiology (5958)
- Plant Biology (12147)
- Synthetic Biology (3401)
- Systems Biology (8237)
- Zoology (1869)