Identification of the Effects of 5-Azacytidine on Porcine Circovirus Type 2 Replication in Porcine Kidney Cells

Simple Summary Porcine circovirus type 2 (PCV2) infection can cause immunosuppression in pigs, create conditions for other virus infections, and bring serious economic losses to the pig industry. 5-Azacytidine (5-Aza) is a potent inhibitor of DNA methylation. In this study, we focused on the effects of 5-Aza on PCV2 infection in porcine kidney cells (PK15 cells). We found that 5-Aza could activate cell apoptosis and inflammatory factors and promote PCV2 replication through the MAPK signaling pathway.Abstract Porcine circovirus type 2 (PCV2) is the main pathogen causing post-weaning multisystemic wasting syndrome (PMWS), which mainly targets the body's immune system and poses a serious threat to the global pig industry. 5-Azacytidine is a potent inhibitor of DNA methylation, which can participate in many important physiological and pathological processes, including virus-related processes, by inhibiting gene expression. However, the impact of 5-Aza on PCV2 replication in cells is not yet clear. We explored the impact of 5-Aza on PCV2 infection utilizing PK15 cells as a cellular model. Our objective was to gain insights that could potentially offer novel therapeutic strategies for PCV2. Our results showed that 5-Aza significantly enhanced the infectivity of PCV2 in PK15 cells. Transcriptome analysis revealed that PCV2 infection activated various immune-related signaling pathways. 5-Aza may activate the MAPK signaling pathway to exacerbate PCV2 infection and upregulate the expression of inflammatory and apoptotic factors.