ACE2 expression and localization are regulated by CFTR: implications beyond cystic fibrosis

Bezzerri, V.; Gentili, V.; Api, M.; Finotti, A.; Papi, C.; Tamanini, A.; Olioso, D.; Duca, M.; Tedesco, E.; Leo, S.; Borgatti, M.; Volpi, S.; Pinton, P.; Cabrini, G.; Gambari, R.; Blasi, F.; Lippi, G.; Rimessi, A.; Rizzo, R.; cipolli, m.

doi:10.1101/2021.11.19.469220

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bioRxiv · 10.1101/2021.11.19.469220

ACE2 expression and localization are regulated by CFTR: implications beyond cystic fibrosis

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Abstract

As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis (CF) could be considered a comorbidity for coronavirus disease 2019 (COVID-19)1. Instead, CF seems to constitute an advantage in COVID-19 infection2-5. To clarify whether host factors expressed by the CF epithelia may influence COVID-19 progression, we investigated the expression of SARS-CoV-2 receptor and coreceptors in primary airway epithelial cells. We found that angiotensin converting enzyme 2 (ACE2) expression and localization are regulated by cystic fibrosis transmembrane conductance regulator (CFTR) channels. Consistently, our results indicate that dysfunctional CFTR channels alter susceptibility to SARS-CoV-2 infection, resulting in reduced viral infection in CF cells. Depending on the pattern of ACE2 expression, the SARS-CoV-2 spike (S) protein induced high levels of Interleukin (IL)-6 in healthy donor-derived primary airway epithelial cells but a very weak response in primary CF cells. Collectively, these data support the hypothesis that CF condition is unfavorable for SARS-CoV-2 infection.

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Bezzerri, V., Gentili, V., Api, M., Finotti, A., Papi, C., Tamanini, A., Olioso, D., Duca, M., Tedesco, E., Leo, S., Borgatti, M., Volpi, S., Pinton, P., Cabrini, G., Gambari, R., Blasi, F., Lippi, G., Rimessi, A., Rizzo, R., cipolli, m.. 2021-11-22. ACE2 expression and localization are regulated by CFTR: implications beyond cystic fibrosis. https://doi.org/10.1101/2021.11.19.469220

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