Modelling SARS-CoV-2 infection in a human alveolus microphysiological system

Suligoj T, Coombes N, Booth C, Savva G, Bewley K, Funnell S, Juge N. (2024)

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The coronavirus 2019 pandemic has highlighted the importance of physiologically relevant in vitro models to assist preclini-cal research. Here, we describe the adaptation of a human alveolus microphysiological system (MPS) model consisting ofprimary human alveolar epithelial and lung microvascular endothelial cells to study infection with SARS-CoV-2 at BiosafetyLevel 3 facility. This infection model recapitulates breathing-like stretch and culture of epithelial cells at the airliquid interfaceand resulted in clinically relevant cytopathic effects including cell rounding of alveolar type 2 cells and disruption of the tightjunction protein occludin. Viral replication was confirmed by immunocytochemical nucleocapsid staining in the epitheliumand increased shedding of SARS-CoV-2 virus within 2 days post-infection, associated with changes in innate host immuneresponses. Together, these data demonstrate that, under the experimental conditions used in this work, this human alveolusMPS chip can successfully model SARS-CoV-2 infection of human alveolar lung cells


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