CircLSM14A regulates PEDV replication via the miR-27b-5p/HMGB1 axis

Circular RNAs (circRNAs) play crucial roles in various physiological and pathological processes, including the complex interactions between viruses and hosts. However, the regulatory mechanism by which porcine milk exosome-derived circRNAs affect porcine epidemic diarrhea virus (PEDV) replication remains poorly understood. Building on our previous sequencing analysis of non-coding RNAs in porcine milk exosomes, we identified circRNA molecules that may regulate PEDV replication in the intestines of piglets and validated these findings at both the cellular and piglet intestinal organoid levels. The results demonstrated that circLSM14A was present in porcine milk exosomes, acted as an endogenous miR-27b-5p sponge, and sequestered and inhibited miR-27b-5p activity. This inhibition increased the expression of high mobility group protein 1 (HMGB1), which subsequently promoted the expression of downstream signaling molecules, including TLR4, NF-κB1, NF-κB2, Rel, and Beclin1, and ultimately enhanced PEDV replication at cellular and intestinal organoid levels. This study identifies circLSM14A as one of the regulators involved in PEDV replication in porcine milk exosomes. These findings advance our understanding of the biological functions of circLSM14A and clarify the role of non-coding RNAs carried by milk exosomes in regulating PEDV replication. This research provides new insights and approaches for the prevention and control of PEDV.