Human Intestinal Organoids Recapitulate Enteric Infections of Enterovirus and Coronavirus

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.

Automated summary

Optimized human intestinal organoids can better simulate enterovirus and coronavirus infections, with significantly more susceptibility to EV-A71 than CVA16. The dynamics of virus-host interaction differ between SARS-CoV and SARS-CoV-2, with SARS-CoV triggering minimal cellular response and SARS-CoV-2 eliciting a moderate cellular response, shedding light on the distinct pathogenicity of these viral pathogens.