PRRSV disrupted nasal mucosal homeostasis by initiating Notch signaling to induce goblet cell differentiation

The porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious swine pathogen that can induce respiratory distress. Mucus is a crucial component of the mucosal defense layer. However, excessive mucus secretion in the airway can disrupt mucosal homeostasis and contribute to airway disease. PRRSV has the ability to replicate and spread within the nasal mucosa. Currently, the effects of PRRSV infection on nasal mucosal barrier remain to be determined. In this study, we provide evidence that PRRSV predominantly targets the posterior region of the porcine nasal cavity and further compromises the integrity of the nasal barrier by disrupting the epithelial tight junctions, upregulating the inflammatory cytokines, and promoting the mucins production. Moreover, there is a significant increase in the number of goblet cells in the nasal cavity of PRRSV-infected piglets, which are responsible for the secretion of mucins and inflammatory cytokines in the airway. Our findings also reveal that PRRSV infection activates the Notch signaling, contributing to the differentiation of goblet cells from progenitor cells. Taken together, this study offers a novel pathogenic mechanisms underlying the severe respiratory symptoms induced by PRRSV.