Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg 69120, Germany; Research Group "Cellular polarity and viral infection," German Cancer Research Center (DKFZ), Heidelberg 69120, Germany.
Research Group "Cellular polarity and viral infection," German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Department of Infectious Diseases, Virology, Heidelberg University, Heidelberg 69120, Germany.
Cell Rep. 2020 Jul 7;32(1):107863. doi: 10.1016/j.celrep.2020.107863. Epub 2020 Jun 19.
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 型（SARS-CoV-2）是一个前所未有的全球健康问题，需要采取协调一致的全球方法来阻止 2019 年冠状病毒病（COVID-19）大流行。虽然 SARS-CoV-2 主要靶向肺上皮细胞，但越来越多的证据表明肠道上皮细胞也会被感染。在这里，我们使用结肠来源的细胞系和原代非转化结肠类器官，首次全面分析了 SARS-CoV-2 在人肠道上皮细胞（hIECs）中的生命周期。我们的结果表明，hIECs 完全支持 SARS-CoV-2 的感染、复制和新产生的感染性病毒颗粒。我们发现，病毒感染会引发极其强烈的固有免疫反应，干扰素介导的反应能有效控制 SARS-CoV-2 的复制和新产生的病毒。总之，我们的数据表明，hIECs 是 SARS-CoV-2 复制的有效部位，并表明 SARS-CoV-2 的肠道阶段可能通过增加患者病毒血症和加剧细胞因子反应，参与 COVID-19 患者观察到的病理变化。
