{"paper_id":"4c4203f9-b91a-4cec-9ff8-677b432e5fea","body_text":"Full text loading...\nAbstract\nThe COVID-19 pandemic has highlighted the importance of physiologically relevant in vitro models to assist preclinical research. Here, we describe the adaptation of a human alveolus microphysiological system (MPS) model consisting of primary human alveolar epithelial and lung microvascular endothelial cells to study infection with SARS-CoV-2 at Biosafety Level 3 (BSL3) facility. This infection model recapitulates breathing-like stretch and culture of epithelial cells at the air-liquid interface (ALI) and resulted in clinically relevant cytopathic effects including cell rounding of alveolar type 2 cells (AT2) and disruption of the tight junction protein occludin (OCLN). Viral replication was confirmed by immunocytochemical nucleocapsid staining in the epithelium and increased shedding of SARS-CoV-2 virus within two days post-infection, associated with changes in innate host immune responses. Together, these data demonstrate that, under the experimental conditions used in this work, this human alveolus MPS chip can successfully model SARS-CoV-2 infection of human alveolar lung cells.\n- Received:\n- Version Posted:\nFunding\n-\nU.S. Food and Drug Administration\n(Award 75F40120C00085)\n- Principal Award Recipient: Simon GP Funnell\n-\nBiotechnology and Biological Sciences Research Council\n(Award BB/CCG2260/1)\n- Principal Award Recipient: George M. Savva","source_license":"CC-BY-4.0","license_restricted":false}