Human Intestinal Organoids Recapitulate Enteric Infections of Enterovirus and Coronavirus

Stem Cell Reports. 2021 Mar 9;16(3):493-504. doi: 10.1016/j.stemcr.2021.02.009. Epub 2021 Feb 12.


Enteroviruses, such as EV-A71 and CVA16, mainly infect the human gastrointestinal tract. Human coronaviruses, including SARS-CoV and SARS-CoV-2, have been variably associated with gastrointestinal symptoms. We aimed to optimize the human intestinal organoids and hypothesize that these optimized intestinal organoids can recapitulate enteric infections of enterovirus and coronavirus. We demonstrate that the optimized human intestinal organoids enable better simulation of the native human intestinal epithelium, and that they are significantly more susceptible to EV-A71 than CVA16. Higher replication of EV-A71 than CVA16 in the intestinal organoids triggers a more vigorous cellular response. However, SARS-CoV and SARS-CoV-2 exhibit distinct dynamics of virus-host interaction; more robust propagation of SARS-CoV triggers minimal cellular response, whereas, SARS-CoV-2 exhibits lower replication capacity but elicits a moderate cellular response. Taken together, the disparate profile of the virus-host interaction of enteroviruses and coronaviruses in human intestinal organoids may unravel the cellular basis of the distinct pathogenicity of these viral pathogens.

Keywords: CVA16; EV-A71; SARS-CoV; SARS-CoV-2; intestinal organoids; pathogenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COVID-19 / virology*
  • Cell Line
  • Chlorocebus aethiops
  • Enterovirus A, Human / pathogenicity*
  • Enterovirus Infections / virology*
  • Host Microbial Interactions / physiology
  • Humans
  • Intestinal Mucosa / virology
  • Intestines / virology*
  • Organoids / virology*
  • SARS-CoV-2 / pathogenicity*
  • Vero Cells
  • Virus Replication / physiology