Measles virus activates NF-kappa B and STAT transcription factors and production of IFN-alpha/beta and IL-6 in the human lung epithelial cell line A549

Epithelial cells of the respiratory tract are the primary targets of measle s virus (MV) infection. In this work we have studied the effect of MV infec tion on the activation of transcription factors nuclear factor (NF)-kappaB and signal transducer and activator of transcription (STAT) and the product ion 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 inhibit ed by the protein synthesis inhibitor cycloheximide, suggesting that MV dir ectly activates NF-kappaB. In contrast, Stall, Stat3, and interferon-stimul ated gene factor 3 (ISGF3) DNA binding was induced by MV infection with del ayed kinetics compared to NF-kappaB activation. MV infection also resulted in an efficient interferon (IFN)-alpha/beta and interleukin-6 production. C ycloheximide and neutralizing anti-IFN-alpha/beta antibodies inhibited MV-i nduced activation of Stall, Stat3, and ISGF3 DNA binding in A549 cells. In conclusion, the results suggest that MV infection activates transcription f actors involved in the initiation of innate immune responses in epithelial cells by two different mechanisms: directly by leading to NF-kappaB activat ion and indirectly via IFN-alpha/beta leading to STAT activation. (C) 2001 Academic Press.