Requirement of NOX2 and Reactive Oxygen Species for Efficient RIG-I-Mediated Antiviral Response through Regulation of MAVS Expression

• Published in: PLoS pathogens Vol. 6; no. 6; p. e1000930
• Main Authors: Soucy-Faulkner, Anton, Mukawera, Espérance, Fink, Karin, Martel, Alexis, Jouan, Loubna, Nzengue, Yves, Lamarre, Daniel, Vande Velde, Christine, Grandvaux, Nathalie
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.06.2010; Public Library of Science (PLoS)
• Subjects: adaptor proteins; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Antimicrobial peptides; Apoptosis; Blotting, Western; Bronchi - cytology; Bronchi - immunology; Bronchi - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Biology/Cell Signaling; Cells, Cultured; CYBB protein; Cytoplasm; Data processing; DEAD Box Protein 58; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; DNA helicase; Enzymes; Epithelial cells; Experiments; Gene expression; Gene Expression Regulation; Gene regulation; Humans; Immune response; Immune system; Immunity; Immunity, Innate; Immunology/Innate Immunity; Infectious Diseases/Viral Infections; Interferon regulatory factor 3; Interferon Regulatory Factor-3 - genetics; Interferon Regulatory Factor-3 - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Kinases; Luciferases - metabolism; Lung Neoplasms - immunology; Lung Neoplasms - metabolism; Lung Neoplasms - virology; Medical research; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Mitochondria; Molecular Biology/Translational Regulation; NAD(P)H oxidase; NADPH Oxidase 2; NADPH Oxidases - genetics; NADPH Oxidases - metabolism; nucleic acids; Oxidases; Pathogens; Physiological aspects; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Receptors, Immunologic; Replication; Respiratory tract; Respirovirus Infections - immunology; Respirovirus Infections - metabolism; Respirovirus Infections - virology; Reverse Transcriptase Polymerase Chain Reaction; RNA viruses; RNA, Messenger - genetics; RNA-Binding Proteins; Sendai virus - physiology; Signal Transduction; Transcription; Transcription factors; Viruses; Canada
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1000930

The innate immune response is essential to the host defense against viruses, through restriction of virus replication and coordination of the adaptive immune response. Induction of antiviral genes is a tightly regulated process initiated mainly through sensing of invading virus nucleic acids in the cytoplasm by RIG-I like helicases, RIG-I or Mda5, which transmit the signal through a common mitochondria-associated adaptor, MAVS. Although major breakthroughs have recently been made, much remains unknown about the mechanisms that translate virus recognition into antiviral genes expression. Beside the reputed detrimental role, reactive oxygen species (ROS) act as modulators of cellular signaling and gene regulation. NADPH oxidase (NOX) enzymes are a main source of deliberate cellular ROS production. Here, we found that NOX2 and ROS are required for the host cell to trigger an efficient RIG-I-mediated IRF-3 activation and downstream antiviral IFNbeta and IFIT1 gene expression. Additionally, we provide evidence that NOX2 is critical for the expression of the central mitochondria-associated adaptor MAVS. Taken together these data reveal a new facet to the regulation of the innate host defense against viruses through the identification of an unrecognized role of NOX2 and ROS.