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 measles virus (MV) infection. In this work we have studied the effect of MV infection on the activation of transcription factors nuclear factor (NF)-kappa B and signal transducer and activator of transcription (STAT) and the production of cytokines in the lung epithelial A549 cell line. NF-kappa B and STAT activation were induced by MV in A549 cells as analyzed by electrophoretic mobility shift assay. NF-kappa B activation was rapid and it was not inhibited by the protein synthesis inhibitor cycloheximide, suggesting that MV directly activates NF-kappa B. In contrast, Stat1, Stat3, and interferon-stimulated gene factor 3 (ISGF3) DNA binding was induced by MV infection with delayed kinetics compared to NF-kappa B 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 Stat1, 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-kappa B activation and indirectly via IFN-alpha/beta leading to STAT activation.
Helin
E
E
Department of Virology, University of Turku, Kiinamyllynkatu 13, FIN-20520 Turku, Finland. eija.helin@utu.fi
Vainionpää
R
R
Hyypiä
T
T
Julkunen
I
I
Matikainen
S
S
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D015870:Gene Expression; D006801:Humans; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000096:biosynthesis*; D016899:Interferon-beta / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D007700:Kinetics; D008459:Measles virus / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D019590:Nucleocapsid Proteins / Q000235:genetics; D012367:RNA, Viral; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D029082:Sendai virus / Q000502:physiology; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*; D051996:Transcription Factor RelA; D014157:Transcription Factors / Q000378:metabolism; D014709:Vero Cells; D014764:Viral Proteins / Q000096:biosynthesis
D004268:DNA-Binding Proteins; C494227:IRF9 protein, human; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; D015850:Interleukin-6; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D019590:Nucleocapsid Proteins; D012367:RNA, Viral; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014764:Viral Proteins; D016899:Interferon-beta; D004247:DNA