ABSTRACT Porcine epidemic diarrhea virus (PEDV) is emerging as a major threat to the global swine industry. Clinical PEDV infection is associated with severe intestinal lesions, resulting in absorptive dysfunction and high mortality rates in suckling piglets. The extracellular matrix (ECM) is an important component of intestinal tissue, providing a structural framework and conveying tissue-specific signals to nearby enterocytes. In this study, we investigated the extensive ECM remodeling observed in intestinal epithelial cells infected with PEDV and elucidated the associated activated ECM receptor-related pathways. Protein-protein interaction network analysis revealed two significantly differentially expressed genes (cluster of differentiation 44 [ CD44 ] and serpin family E member 1 [ SERPINE1 ]) associated with the ECM. At the transcriptional level, both genes exhibited significant positive correlation with the extent of PEDV replication. Similarly, the expression of CD44 and PAI-1 (encoded by SERPINE1 ) was also increased in the intestines of piglets during viral infection. Furthermore, CD44 exhibited antiviral activity by enhancing the expression of antiviral cytokines (e.g., interleukin [IL]-6, IL-18, IL-11, and antimicrobial peptide beta-defensin 1) by activating nuclear factor-κB signaling. Conversely, PAI-1 was found to promote the release of progeny virions during PEDV infection, despite a decreased intracellular viral load. Nevertheless, the underlying mechanisms are still unclear. Taken together, our results highlighted the biological roles of specific ECM-regulated genes, i.e., CD44 and SERPINE1 in suppressing and promoting PEDV infection, thereby providing a theoretical foundation for the role of the ECM in intestinal infections and identifying potential therapeutic targets for PEDV.
【저자키워드】 viral replication, Porcine epidemic diarrhea virus, Extracellular matrix, cluster of differentiation 44, serpin family E member 1, viral release, 【초록키워드】 viral infection, Infection, antiviral activity, virus, Replication, Viral load, clinical, intestine, Cluster, network analysis, expression, mechanism, differentially expressed gene, Signaling, Interaction, Pathways, ECM, enterocytes, epidemic diarrhea, dysfunction, structural framework, positive correlation, lesions, PEDV, SERPINE1, high mortality rate, transcriptional level, potential therapeutic target, antimicrobial peptide, intestinal tissue, IL-18, nuclear, CD44, Genes, intestinal, resulting, significantly, investigated, exhibited, activated, promote, progeny virion, activating, intestinal epithelial cell, antiviral cytokine, IL-11, 【제목키워드】 virus infection, Signaling, epidemic diarrhea, role, intestinal, Extracellular,