Influenza virus activates inflammasomes via its intracellular M2 ion channel

Autor: Iris K. Pang, Takeshi Ichinohe, Akiko Iwasaki
Rok vydání: 2010
Předmět:
Viral pathogenesis
Immunology
Orthomyxoviridae
Golgi Apparatus
Virus Replication
Ion Channels
Article
Virus
Potassium Chloride
Viral Matrix Proteins
Mice
03 medical and health sciences
0302 clinical medicine
Orthomyxoviridae Infections
NLR Family
Pyrin Domain-Containing 3 Protein
medicine
Animals
Immunology and Allergy
Monensin
Cells
Cultured
Sequence Deletion
030304 developmental biology
Mice
Knockout
0303 health sciences
Membrane Glycoproteins
Viral matrix protein
biology
Macrophages
Inflammasome
RNA virus
Dendritic Cells
Oncogene Proteins
Viral
Hydrogen-Ion Concentration
biology.organism_classification
Virology
3. Good health
Cell biology
Mice
Inbred C57BL
Protein Transport
Toll-Like Receptor 7
Viral replication
Cytokines
Protons
Carrier Proteins
Genetic Engineering
Intracellular
030215 immunology
medicine.drug
Zdroj: Nature immunology
ISSN: 1529-2916
1529-2908
DOI: 10.1038/ni.1861
Popis: Influenza virus, a negative-stranded RNA virus that causes severe illness in humans and animals, stimulates the inflammasome through the Nod-like receptor NLRP3. However, the mechanism by which influenza virus activates the NLRP3 inflammasome is unknown. Here we show that the influenza virus M2 protein, a proton-selective ion channel important in viral pathogenesis, stimulates the NLRP3 inflammasome pathway. M2 channel activity was required for the activation of inflammasomes by influenza and was sufficient to activate inflammasomes in primed macrophages and dendritic cells. M2-induced activation of inflammasomes required its localization to the Golgi apparatus and was dependent on the pH gradient. Our results show a mechanism by which influenza virus infection activates inflammasomes and identify the sensing of disturbances in intracellular ionic concentrations as a previously unknown pathogen-recognition pathway.
Databáze: OpenAIRE
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