Document Detail


Requirement of NOX2 and reactive oxygen species for efficient RIG-I-mediated antiviral response through regulation of MAVS expression.
MedLine Citation:
PMID:  20532218     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Anton Soucy-Faulkner; Espérance Mukawera; Karin Fink; Alexis Martel; Loubna Jouan; Yves Nzengue; Daniel Lamarre; Christine Vande Velde; Nathalie Grandvaux
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-03
Journal Detail:
Title:  PLoS pathogens     Volume:  6     ISSN:  1553-7374     ISO Abbreviation:  PLoS Pathog.     Publication Date:  2010  
Date Detail:
Created Date:  2010-06-10     Completed Date:  2010-10-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101238921     Medline TA:  PLoS Pathog     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e1000930     Citation Subset:  IM    
Affiliation:
CRCHUM - Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / genetics*,  metabolism
Blotting, Western
Bronchi / cytology,  immunology*,  metabolism
Carrier Proteins / genetics,  metabolism
Cells, Cultured
DEAD-box RNA Helicases / genetics,  metabolism*
Gene Expression Regulation*
Humans
Immunity, Innate
Interferon Regulatory Factor-3 / genetics,  metabolism
Interleukin-6 / genetics,  metabolism
Luciferases / metabolism
Lung Neoplasms / immunology*,  metabolism,  virology
Membrane Glycoproteins / genetics,  metabolism*
NADPH Oxidase / genetics,  metabolism*
RNA, Messenger / genetics
Reactive Oxygen Species / metabolism*
Respirovirus Infections / immunology,  metabolism,  virology
Reverse Transcriptase Polymerase Chain Reaction
Sendai virus / physiology
Signal Transduction
Grant Support
ID/Acronym/Agency:
MOP#89807//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/CYBB protein, human; 0/Carrier Proteins; 0/IFIT1 protein, human; 0/Interferon Regulatory Factor-3; 0/Interleukin-6; 0/Membrane Glycoproteins; 0/RNA, Messenger; 0/Reactive Oxygen Species; 0/VISA protein, human; EC 1.13.12.-/Luciferases; EC 1.6.3.1/NADPH Oxidase; EC 3.6.1.-/DDX58 protein, human; EC 3.6.1.-/DEAD-box RNA Helicases
Comments/Corrections

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