Porcine circovirus type 2 (PCV2) is the major etiological agent responsible for post-weaning multisystemic wasting syndrome (PMWS), a disease that disrupts immune functions and continues to threaten the global swine population. 5-Azacytidine (5-Aza), a recognized inhibitor of DNA methyltransferase activity, can modulate numerous biological and pathological events, including those associated with viral infections, through the suppression of gene transcription. Yet, its influence on PCV2 replication remains unclear. In the present work, PK15 porcine kidney cells were employed to assess how 5-Aza affects PCV2 infection. The results indicated that 5-Aza treatment substantially increased PCV2 infectivity in these cells. Transcriptomic profiling showed that PCV2 infection activates multiple immune-related signaling routes, while 5-Aza may intensify infection via MAPK pathway activation, promoting inflammatory and apoptotic gene expression. These findings may provide new perspectives for the therapeutic management of PCV2.
