Porcine arterivirus activates the NF-κB pathway through IκB degradation

Nuclear factor-kappaB (NF-kappa B) is a critical regulator of innate and adaptive immune function as well as cell proliferation and survival. The present study demonstrated for the first time that a virus belonging to the Arteriviridae family activates NF-kappa B in MARC-145 cells and alveolar macrophages. In porcine reproductive and respiratory syndrome virus (PRRSV)-infected cells, NF-kappa B activation was characterized by translocation of NF-kappa B from the cytoplasm to the nucleus, increased DNA binding activity, and NF-kappa B-regulated gene expression. NF-kappa B activation was increased as PRRSV infection progressed and in a viral dose-dependent manner. UV-inactivation of PRRSV significantly reduced the level of NF-kappa B activation. Degradation Of I kappa B protein was detected late in PRRSV infection, and overexpression of the dominant negative form of I kappa B alpha (I kappa B alpha DN) significantly suppressed NF-kappa B activation induced by PRRSV. However, I kappa B alpha DN did not affect viral replication and viral cytopathic effect. PRRSV infection induced oxidative stress in cells by generating reactive oxygen species (ROS), and antioxidants inhibited NF-kappa B DNA binding activity in PRRSV-infected cells, suggesting ROS as a mechanism by which NF-kappa B was activated by PRRSV infection. Moreover, NF-kappa B-dependent expression of matrix metalloproteinase (MMP)-2 and MMP-9 was observed in PRRSV-infected cells, an observation which implies that NF-kappa B activation is a biologically significant aspect of PRRSV pathogenesis. The results presented here provide a basis for understanding molecular pathways of pathology and immune evasion associated with disease caused by PRRSV (c) 2005 Elsevier Inc. All rights reserved.