Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / metabolism
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Blotting, Western
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Bronchi / cytology
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Bronchi / immunology*
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Bronchi / metabolism
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cells, Cultured
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DEAD Box Protein 58
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism*
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Gene Expression Regulation*
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Humans
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Immunity, Innate
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Interferon Regulatory Factor-3 / genetics
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Interferon Regulatory Factor-3 / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Luciferases / metabolism
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Lung Neoplasms / immunology*
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Lung Neoplasms / metabolism
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Lung Neoplasms / virology
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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NADPH Oxidase 2
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NADPH Oxidases / genetics
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NADPH Oxidases / metabolism*
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RNA, Messenger / genetics
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RNA-Binding Proteins
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Reactive Oxygen Species / metabolism*
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Receptors, Immunologic
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Respirovirus Infections / immunology
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Respirovirus Infections / metabolism
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Respirovirus Infections / virology
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Reverse Transcriptase Polymerase Chain Reaction
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Sendai virus / physiology
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Signal Transduction
Substances
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Adaptor Proteins, Signal Transducing
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Carrier Proteins
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IFIT1 protein, human
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Interferon Regulatory Factor-3
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Interleukin-6
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MAVS protein, human
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Membrane Glycoproteins
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RNA, Messenger
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RNA-Binding Proteins
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Reactive Oxygen Species
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Receptors, Immunologic
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Luciferases
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CYBB protein, human
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NADPH Oxidase 2
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NADPH Oxidases
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RIGI protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases