title: Highly pathogenic influenza viruses inhibit inflammatory response in monocytes via activation of rar-related orphan receptor RORα.
abstract: Infections with highly pathogenic avian influenza viruses (HPAIV) in humans lead to systemic disease associated with cytokine storm and multiorgan failure. In this study we aimed to identify the role of monocytes for the host response to HPAIV infection. Using genome-wide microarray analysis, we surprisingly demonstrate a reduced immune response of human monocytes to HPAIV H5N1 compared to human influenza A viruses. In bioinformatic analyses we could reveal a potential role of the Rar-related orphan receptor alpha (RORα) for the gene expression pattern induced by H5N1. RORα is known as an inhibitor of NF-κB signaling. We provide evidence that in monocytes RORα is activated by H5N1, resulting in inhibited NF-κB signaling. Using murine Hoxb8-immortalized RORα⁻/⁻, monocytes rescued NF-κB signaling upon H5N1 infection, confirming the biological relevance of RORα as an H5N1-induced mediator of monocytic immunosuppression. In summary, our study reveals a novel RORα-dependent escape mechanism by which H5N1 prevents an effective inflammatory response of monocytes blocking NF-κB-dependent gene expression.
authors: Institute of Immunology, University of Münster, Münster, Germany. Friesenhagen.Judith @ mh-hannover.de
authors: Judith
authors: J
authors: Friesenhagen
authors: Dorothee
authors: D
authors: Viemann
authors: Yvonne
authors: Y
authors: Börgeling
authors: Mirco
authors: M
authors: Schmolke
authors: Christoph
authors: C
authors: Spiekermann
authors: Susanne
authors: S
authors: Kirschnek
authors: Stephan
authors: S
authors: Ludwig
authors: Johannes
authors: J
authors: Roth
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002461:Cell Line, Transformed; D019295:Computational Biology; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D006801:Humans; D007109:Immunity / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000235:genetics / Q000276:immunology*; D051379:Mice; D046228:Microarray Analysis; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D016328:NF-kappa B / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000956:Antigens, Viral; D016328:NF-kappa B; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human