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Cell Rep
. 2020 Jun 19;107863.
doi: 10.1016/j.celrep.2020.107863. Online ahead of print.
Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells
Megan L Stanifer 1 , Carmon Kee 2 , Mirko Cortese 3 , Camila Metz Zumaran 4 , Sergio Triana 5 , Markus Mukenhirn 4 , Hans-Georg Kraeusslich 4 , Theodore Alexandrov 6 , Ralf Bartenschlager 7 , Steeve Boulant 8
AffiliationsExpand
- PMID: 32610043
- PMCID: PMC7303637
- DOI: 10.1016/j.celrep.2020.107863
Abstract
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: IFN; ISGs; SARS-CoV-2; human intestinal epithelial cells; interferon; interferon lambda; interferon stimulted genes; intrinsic immunity; organoids.