Expression of influenza virus hemagglutinin activates transcription factor NF-kappa B.
Influenza virus infection initiates transcription of a variety of genes for cytokines such as tumor necrosis factor alpha (TNF-alpha), TNF-beta, interleukin 1 alpha, (IL-1 alpha), IL-1 beta, IL-2, IL-4, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, and gamma interferon. However, the mechanism by which virus infection elicits cytokine expression remains unknown. Six influenza virus-induced cytokine genes are targets for the inducible transcription factor NF-kappa B, a central regulator of the human immune response. Here, we show that expression of a single influenza virus protein, the virion surface hemagglutinin, strongly activates NF-kappa B DNA binding and transactivation. Activation is inhibited in the presence of the antioxidant dithiothreitol, suggesting that, similar to the findings for previously described inducers of NF-kappa B, hemagglutinin expression generates radical oxygen intermediates which activate the transcription factor. Hemagglutinin is the first secretory and structural viral protein reported to activate NF-kappa B and thus represents a new class of inducers for this transcription factor. We discuss these results in the context of clinical complications of influenza virus infection.
Biochemical Institute, University of Freiburg, Germany.
H L
HL
Pahl
P A
PA
Baeuerle
D000975:Antioxidants / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D006367:HeLa Cells; D006389:Hemagglutinins, Viral / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000235:genetics*; D007251:Influenza, Human / Q000235:genetics*; D016328:NF-kappa B / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D051841:Transcription Factor RelB; D014157:Transcription Factors; D014158:Transcription, Genetic
D000975:Antioxidants; D006389:Hemagglutinins, Viral; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D051841:Transcription Factor RelB; D004229:Dithiothreitol