Measles virus activates NF-κB and STAT transcription factors and production of IFN-α/β and IL-6 in the human lung epithelial cell line A549

Epithelial cells of the respiratory tract are the primary targets of measles virus (MV) infection. In this work we have studied the effect of MV infection on the activation of transcription factors nuclear factor (NF)-kappaB and signal transducer and activator of transcription (STAT) and the production of cytokines in the lung epithelial A549 cell line. NF-kappaB and STAT activation were induced by MV in A549 cells as analyzed by electrophoretic mobility shift assay. NF-kappaB activation was rapid and it was not inhibited by the protein synthesis inhibitor cycloheximide, suggesting that MV directly activates NF-kappaB. In contrast, Stall, Stat3, and interferon-stimulated gene factor 3 (ISGF3) DNA binding was induced by MV infection with delayed kinetics compared to NF-kappaB activation. MV infection also resulted in an efficient interferon (IFN)-alpha/beta and interleukin-6 production. Cycloheximide and neutralizing anti-IFN-alpha/beta antibodies inhibited MV-induced activation of Stall, Stat3, and ISGF3 DNA binding in A549 cells. In conclusion, the results suggest that MV infection activates transcription factors involved in the initiation of innate immune responses in epithelial cells by two different mechanisms: directly by leading to NF-kappaB activation and indirectly via IFN-alpha/beta leading to STAT activation. (C) 2001 Academic Press.