Foxp3 inhibits PCV2 replication by reducing the ATPase activity of Rep.

Porcine circovirus type 2 (PCV2) is the pathogen that causes porcine circovirus disease, characterized by severe immunosuppression and significant economic losses in the swine industry. The replicase (Rep), one of the most critical non-structural proteins of PCV2, plays a pivotal role in viral replication. However, the mechanism by which Rep regulates the replication of PCV2 still requires further investigation. Our study demonstrated that PCV2 can infect regulatory T cells (Tregs), and within the nucleus, Rep interacted with Foxp3, while the structural protein capsid protein (Cap) did not exhibit this interaction. Further investigations revealed that the Forkhead domain of Foxp3 was crucial for mediating its interaction with the C-terminal region of Rep, which had an ATPase activity-regulating domain. The interaction between Foxp3 and Rep reduced the ATPase activity of Rep, thereby inhibiting PCV2 replication. This study provided a theoretical foundation for elucidating the role of Rep in PCV2 pathogenesis and contributed to a deeper understanding of the molecular mechanisms underlying PCV2 immune evasion.