PEDV infection downregulates goblet cell differentiation through activating the Notch pathway

Area of Science:

• Veterinary Virology
• Gastroenterology
• Cell Biology

Background:

• Porcine epidemic diarrhoea virus (PEDV) is a major swine enteric coronavirus causing significant piglet mortality.
• The precise mechanisms of PEDV-induced intestinal dysfunction and barrier disruption remain incompletely understood.
• Goblet cells are crucial for intestinal barrier function, and their regulation by PEDV is a key area of investigation.

Purpose of the Study:

• To elucidate the molecular mechanisms by which PEDV affects intestinal epithelial cell function and differentiation.
• To investigate the impact of PEDV infection on goblet cell numbers and intestinal barrier integrity in piglets.
• To identify the signaling pathways involved in PEDV-mediated disruption of intestinal homeostasis.

Main Methods:

• Analysis of intestinal tissues from newborn piglets experimentally infected with PEDV.
• In vitro studies utilizing intestinal monolayer organoid models.
• Investigation of key signaling pathways including Notch, MAPK, and Wnt/β-catenin.
• Assessment of goblet cell differentiation and intestinal barrier integrity markers.

Main Results:

• PEDV infection significantly reduced goblet cell numbers and compromised intestinal barrier integrity in piglets.
• PEDV infection activated the Notch and MAPK signaling pathways while concurrently suppressing the Wnt/β-catenin pathway in the piglet intestine.
• In vitro organoid models demonstrated that PEDV hinders goblet cell differentiation via Notch pathway activation.
• The PEDV ORF3 protein was identified as a key mediator in activating the Notch pathway and inhibiting goblet cell differentiation.

Conclusions:

• PEDV infection disrupts intestinal mucosal barrier integrity by reducing goblet cells, a process mediated by specific signaling pathways.
• The Notch signaling pathway plays a critical role in inhibiting goblet cell differentiation during PEDV infection.
• The PEDV ORF3 protein is implicated in the pathogenesis of intestinal barrier dysfunction through Notch pathway activation.