Enteroviruses infect human enteroids and induce antiviral signaling in a cell lineage-specific manner

Area of Science:

• Virology
• Gastroenterology
• Cell Biology

Background:

• Enteroviruses are common human pathogens transmitted via the fecal-oral route.
• The mechanisms of enterovirus infection within the human gastrointestinal tract are not well understood.

Purpose of the Study:

• To investigate enterovirus infection dynamics in the human intestinal epithelium using stem cell-derived enteroids.
• To identify specific intestinal cell types susceptible to enterovirus infection and characterize host responses.

Main Methods:

• Utilized human small intestinal enteroids derived from stem cells to model enterovirus infection.
• Exposed enteroids to various enteroviruses, including echovirus 11 (E11), coxsackievirus B (CVB), and enterovirus 71 (EV71).
• Employed the Notch inhibitor dibenzazepine (DBZ) to induce differentiation and assess cell-specific permissiveness.

Main Results:

• Enteroids supported infection by diverse enteroviruses, unlike immortalized cell lines.
• Enteroids mounted virus-specific antiviral and inflammatory signaling pathways upon infection.
• Goblet cells demonstrated resistance to E11 infection, while enteroendocrine cells were permissive.

Conclusions:

• Human intestinal enteroids serve as a valuable model for studying enterovirus infections.
• Enteroviruses exhibit tropism for specific intestinal cell populations, such as enteroendocrine cells.
• Findings may facilitate the development of novel therapeutic strategies against enterovirus infections.