Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) causes coronavirus disease 2019 (COVID‐19), which may result in acute respiratory distress syndrome (ARDS), multiorgan failure, and death. The alveolar epithelium is a major target of the virus, but representative models to study virus host interactions in more detail are currently lacking. Here, we describe a human 2D air–liquid interface culture system which was characterized by confocal and electron microscopy and single‐cell mRNA expression analysis. In this model, alveolar cells, but also basal cells and rare neuroendocrine cells, are grown from 3D self‐renewing fetal lung bud tip organoids. These cultures were readily infected by SARS‐CoV‐2 with mainly surfactant protein C‐positive alveolar type II‐like cells being targeted. Consequently, significant viral titers were detected and mRNA expression analysis revealed induction of type I/III interferon response program. Treatment of these cultures with a low dose of interferon lambda 1 reduced viral replication. Hence, these cultures represent an experimental model for SARS‐CoV‐2 infection and can be applied for drug screens.

中文翻译：

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用于类人II型肺泡细胞SARS-CoV-2感染的类器官源性支气管肺泡模型

严重的急性呼吸综合症冠状病毒2（SARS-CoV-2）导致2019年的冠状病毒病（COVID-19），可能导致急性呼吸窘迫综合症（ARDS），多器官衰竭和死亡。肺泡上皮是该病毒的主要靶标，但目前尚缺乏用于更详细研究病毒宿主相互作用的代表性模型。在这里，我们描述了人类2D气液界面培养系统，其特征在于共聚焦和电子显微镜以及单细胞mRNA表达分析。在此模型中，肺泡细胞，以及基础细胞和稀有的神经内分泌细胞，都是从3D自我更新的胎儿肺芽尖端类器官生长出来的。这些培养物很容易被SARS-CoV-2感染，主要针对的是表面活性剂蛋白C阳性的II型肺泡样细胞。所以，检测到显着的病毒滴度，并且mRNA表达分析揭示了I / III型干扰素应答程序的诱导。用低剂量的干扰素λ1处理这些培养物可减少病毒复制。因此，这些培养物代表了SARS-CoV-2感染的实验模型，可用于药物筛查。