Cell Reports
Volume 32, Issue 1, 7 July 2020, 107863
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Report
Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells

https://doi.org/10.1016/j.celrep.2020.107863Get rights and content
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Highlights

  • Human intestinal epithelium cells (hIECs) can be infected by SARS-CoV-2

  • hIECs support SARS-CoV-2 replication and produce de novo viruses

  • SARS-CoV-2 infection can be controlled in hIECs by type I and III interferons

Summary

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.

Keywords

SARS-CoV-2
human intestinal epithelial cells
interferon
IFN
interferon lambda
intrinsic immunity
organoids
interferon stimulted genes
ISGs

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