title: Mucosal reactive oxygen species are required for antiviral response: role of Duox in influenza a virus infection.
abstract: OBJECTIVE
  Influenza A virus (IAV), a major airborne pathogen, is closely associated with significant morbidity and mortality. The primary target for influenza virus replication is the respiratory epithelium, which reacts to infection by mounting a multifaceted antiviral response. A part of this mucosal host defense is the generation of reactive oxygen species (ROS) by NADPH oxidases. Duox1 and Duox2 are the main ROS-producing enzymes in the airway epithelium, but their contribution to mammalian host defense is still ill defined.
  
  
  RESULTS
  To gain a better understanding of Duox function in respiratory tract infections, human differentiated lung epithelial cells and an animal model were used to monitor the effect of epithelial ROS on IAV propagation. IAV infection led to coordinated up-regulation of Duox2 and Duox-mediated ROS generation. Interference with H2O2 production and ROS signaling by oxidase inhibition or H2O2 decomposition augmented IAV replication. A nuclear pool of Duox enzymes participated in the regulation of the spliceosome, which is critical for alternative splicing of viral transcripts and controls the assembly of viable virions. In vivo silencing of Duox increased the viral load on intranasal infection with 2009 pandemic H1N1 influenza virus.
  
  
  METHODS
  This is the first study conclusively linking Duox NADPH oxidases with the antiviral mammalian immune response. Further, ROS generated by Duox enzymes localized adjacent to nuclear speckles altered the splicing of viral genes.
  
  
  CONCLUSIONS
  Duox-derived ROS are host protective and essential for counteracting IAV replication.
authors.affiliation: 1 Conway Institute, University College Dublin , Dublin, Ireland .
authors.forename: Monika
authors.initials: M
authors.lastname: Strengert
authors.forename: Richard
authors.initials: R
authors.lastname: Jennings
authors.forename: Suzel
authors.initials: S
authors.lastname: Davanture
authors.forename: Patti
authors.initials: P
authors.lastname: Hayes
authors.forename: Gülsah
authors.initials: G
authors.lastname: Gabriel
authors.forename: Ulla G
authors.initials: UG
authors.lastname: Knaus
mesh_terms: D002460:Cell Line; D000074623:Dual Oxidases; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018928:Immunity, Mucosal; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007251:Influenza, Human / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D019562:Viral Load / Q000187:drug effects
chemical_list: D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000074623:Dual Oxidases; D019255:NADPH Oxidases; C431513:DUOX1 protein, human; C431515:DUOX2 protein, human