Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells

Cell Rep. 2020 Jul 7;32(1):107863. doi: 10.1016/j.celrep.2020.107863. Epub 2020 Jun 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betacoronavirus / growth & development*
  • Betacoronavirus / immunology
  • COVID-19
  • Caco-2 Cells
  • Cell Line, Tumor
  • Colon / cytology
  • Colon / immunology
  • Colon / virology*
  • Coronavirus Infections / immunology
  • Coronavirus Infections / pathology
  • Cytokine Release Syndrome / immunology
  • Cytokine Release Syndrome / virology
  • Cytokines / blood
  • Epithelial Cells / immunology*
  • Epithelial Cells / virology
  • Humans
  • Interferons / immunology*
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / virology
  • Pandemics
  • Pneumonia, Viral / immunology
  • Pneumonia, Viral / pathology
  • SARS-CoV-2
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / pathology
  • Virus Replication / immunology

Substances

  • Cytokines
  • interferon type III
  • Interferons