Curcumin Inhibits Viral Replication and Attenuates PEDV-Induced Intestinal Damage by Modulating Antigen Processing and Presentation in Piglets

The effects and mechanisms of curcumin (CUR) as a feed additive in the repair of porcine epidemic diarrhea virus (PEDV)-caused piglet intestinal injury were investigated. Twenty-four 7-day-old piglets were randomly assigned to Control, CUR, PEDV, and CUR+PEDV groups, with 6 piglets in each group. From Day 4, piglets in the CUR and CUR+PEDV groups were orally administered CUR (5 mg/kg BW). Piglets in the PEDV and CUR+PEDV groups were orally inoculated with PEDV (3×10⁶ TCID₅₀) on the 8th day. On Day 11, blood and intestinal tissue samples were collected from slaughtered piglets. PEDV infection caused severe intestinal damage, whereas CUR significantly improved intestinal morphology and inhibited viral replication. Transcriptome analysis identified 62 CUR-reversed differentially expressed genes (DEGs) in the PEDV-infected jejunum. GO and KEGG enrichment analyses revealed that 62 CUR-reversed DEGs were primarily associated with antigen processing and presentation. The hub genes included MHC class II–related genes (CD74, SLA-DRA, SLA-DQA1, SLA-DQB1, SLA-DMA, SLA-DMB, and SLA-DOA), which regulate adaptive immune responses, and complement-related genes (C1qA, C1qB, and C1qC), which activate the classical complement pathway. In addition, the hub genes also included gene CD4 responsible for identifying MHC-II antigen peptide complexes. qPCR confirmed that CUR mitigated PEDV-induced reductions in SLA-DOA, SLA-DMB, and C1qB mRNA expression in the jejunum, while immunohistochemistry showed increased C1qB protein levels. Collectively, these findings demonstrate that CUR inhibits PEDV replication and attenuates intestinal damage by enhancing both adaptive and innate immune responses in infected piglets, suggesting that CUR can serve as an immune enhancer to improve the piglet intestine’s ability to resist PEDV infection.