Determinants of SARS-CoV-2 and other coronaviruses tropism in 3D models of human pulmonary epithelia

The reasons for the severity of SARS-CoV-2 infection, which induces a case fatality rate above 1% in symptomatic patients, are not understood. Pathological findings indicate that this virus infects airways and lung alveolae, which likely contributes to the severe pneumonia characteristic of the COVID-19 syndrome. However, the determinants responsible for this tropism and the precise nature of the target cells in the human respiratory tract remain to be explored. To this goal, we propose to use 3D culture systems that reproduce the architecture, cellular composition, and functions of pulmonary epithelia.

We will compare the tropism of SARS-CoV-2 and more benign human coronaviruses for primary epithelia of the upper and lower respiratory tract, to determine whether tropism associates with pathogenicity. We will use models based on reconstructed human airway epithelia with fully differentiated ciliary cells, which may express high levels of coronavirus entry cofactors. We will also take advantage of a lung-on-chip technology that mimics the pulmonary alveolae stretch associated with breathing to develop physiologically relevant models of SARS-CoV-2 infection.