Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-Induced Reactive Oxygen Species Inhibit Phagocytosis in Alveolar Macrophages

Porcine reproductive and respiratory syndrome (PRRS) is an immunosuppressive disease caused by PRRS virus (PRRSV). PRRSV infection not only compromises the host immune defenses, but also predisposes the host to secondary infections by other pathogens, of which PRV is one of the common secondary infection pathogens. Porcine alveolar macrophages (PAMs) are the primary target cells of PRRSV, and their phagocytic function is critical for immune defense, homeostasis maintenance, and disease regulation. However, PRRSV disrupts PAMs phagocytosis, impairing the host’s ability to combat infection. This study used PRV-pAb complexes as phagocytic indicators, investigated the effect of PRRSV infection on PAMs phagocytosis and its underlying molecular mechanisms. We found that PRRSV infection interfered with phagosome maturation—a process regulated by Rab7 and other regulators, thereby blocking phagocytic degradation and significantly suppressing PAMs phagocytic activity. Further analysis revealed that reactive oxygen species (ROS) play a key role in this process. Elevated ROS levels damaged lysosomal membrane integrity, ultimately inhibiting phagosome-lysosome fusion. Notably, phagocytosis of PRRSV-infected PAMs was partially restored with N-acetylcysteine (NAC) by reducing ROS levels. These findings offer novel insights into PRRSV-induced immunosuppression and secondary infections while providing a theoretical foundation for developing more effective PRRSV prevention and control strategies.