SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for in vitro/in vivo models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection in vivo . Methods: Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Results: Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. Conclusions: These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.
【저자키워드】 SARS-CoV-2, Infection, human lung, xenograft, humanized mouse model, 【초록키워드】 Treatment, Structure, Vaccine, Pathogenesis, Respiratory failure, Pneumonia, Therapeutics, SARS-COV-2 infection, COVID-19 pandemic, Human, lung, Lung infection, Local, chemokine, Histopathology, Spread, clinical samples, Viral, mice, viral replication, death, epithelial cells, in vivo, SARS-CoV-2 pathogenesis, SARS-CoV-2 replication, COVID-19 patients, structures, epithelial cell, IFN-α, lung damage, target cells, antiviral therapies, target cell, Support, tissue, tissues, growth, These data, life-threatening, lung tissue, pro-inflammatory response, SCID, pathogenesis of SARS-CoV-2, humanized, robust, clinical sample, responsible, evaluate, caused, inhibited, facilitate, replicated, fetal, cytokine/chemokine expression, human lung cell, was tested, were assessed, 【제목키워드】 lung,