title: Duox2 is required for the transcription of pattern recognition receptors in acute viral lung infection: An interferon-independent regulatory mechanism.
abstract: The innate immune response, which constitutes the first line of defense against influenza A virus (IAV) infection, is activated by pattern recognition receptors (PRRs) that recognize viral structures. We found that the PRRs, retinoic acid-inducible gene 1 (RIG-I) and melanoma differentiation-associated protein 5 (MDA5), which have been implicated as interferon (IFN)-stimulated genes, were dominantly responsible for the recognition of IAV in lungs of mice at 3 and 7 days post infection (dpi). Intranasal administration of IFNs enhanced RIG-I and MDA5 gene expression after IAV infection and mRNA levels of RIG-I and MDA5 were significantly reduced at 7 dpi in mice with neutralization of secreted IFNs. However, blockade of IFNs did not alter the transcription of RIG-I and MDA5 at 3 dpi. We studied the antiviral effect of Duox2 in vivo lung to elucidate the role of Duox2 in respiratory mucosa. RIG-I and MDA5 mRNA levels were induced to a lower extent in lungs of mice that were inoculated with Duox2 small hairpin RNA regardless of secreted IFNs at 3 dpi. We propose that Duox2 is responsible for IFN-independent signaling for induction of PRRs transcription and can control acute IAV lung infection at the beginning of infection.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine Korea University, Ansan, South Korea.
authors.forename: Seung-No
authors.initials: SN
authors.lastname: Hong
authors.affiliation: Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Hanna
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Kim
authors.affiliation: Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Tae-Bin
authors.initials: TB
authors.lastname: Won
authors.affiliation: Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Doo Hee
authors.initials: DH
authors.lastname: Han
authors.affiliation: Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Chae-Seo
authors.initials: CS
authors.lastname: Rhee
authors.affiliation: Department of Otorhinolaryngology, Seoul National University College of Medicine, Seoul, South Korea. Electronic address: hyunjerry@snu.ac.kr.
authors.forename: Hyun Jik
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000208:Acute Disease; D000818:Animals; D000074623:Dual Oxidases / Q000235:genetics / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D009980:Influenza A virus / Q000276:immunology / Q000502:physiology; D000072640:Interferon-Induced Helicase, IFIH1 / Q000235:genetics; D007372:Interferons / Q000008:administration & dosage* / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000821:virology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology; D011956:Receptors, Cell Surface; D051192:Receptors, Pattern Recognition / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014779:Virus Replication; D000097905:Roundabout Proteins
chemical_list: D000074623:Dual Oxidases; D000072640:Interferon-Induced Helicase, IFIH1; D007372:Interferons; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D051192:Receptors, Pattern Recognition; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins; C000614831:Duox2 protein, mouse; C510592:Ifih1 protein, mouse
keywords: Acute viral lung infection; Duox2; Influenza A virus; MDA5; RIG-I