Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is an unprecedented worldwide health problem that requires concerted and global approaches to stop the coronavirus 2019 (COVID-19) pandemic. Although SARS-CoV-2 primarily targets lung epithelium cells, there is growing evidence that the intestinal epithelium is also infected. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of the SARS-CoV-2 life cycle in human intestinal epithelial cells (hIECs). Our results demonstrate that hIECs fully support SARS-CoV-2 infection, replication, and production of infectious de novo virus particles. We found that viral infection elicits an extremely robust intrinsic immune response where interferon-mediated responses are efficient at controlling SARS-CoV-2 replication and de novo virus production. Taken together, our data demonstrate that hIECs are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing to increasing patient viremia and fueling an exacerbated cytokine response.

严重急性呼吸综合征相关冠状病毒 2 (SARS-CoV-2) 是一个前所未有的全球健康问题，需要全球采取协调一致的措施来阻止 2019 冠状病毒 (COVID-19) 的大流行。尽管 SARS-CoV-2 主要针对肺上皮细胞，但越来越多的证据表明肠上皮也受到感染。在这里，我们使用结肠源性细胞系和原代未转化的结肠类器官，对人肠上皮细胞 (hIEC) 中的 SARS-CoV-2 生命周期进行了首次全面分析。我们的结果表明，hIEC 完全支持 SARS-CoV-2 感染、复制和感染性从头病毒颗粒的产生。我们发现病毒感染会引发极其强大的内在免疫反应，其中干扰素介导的反应可有效控制 SARS-CoV-2 复制和病毒从头产生。综上所述，我们的数据表明，hIEC 是 SARS-CoV-2 复制的高产位点，并表明 SARS-CoV-2 的肠相可能通过增加患者病毒血症并加剧在 COVID-19 患者中观察到的病理学而参与其中。细胞因子反应加剧。