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PMID: 20383149 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Influenza virus activates inflammasomes via its intracellular M2 ion channel.

Nature immunology ·Vol. 11 ·No. 5 ·2010-05-00 ·Pages 404-10

Ichinohe T, Pang IK, Iwasaki A

Abstract

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.

MeSH Terms
Animals Carrier Proteins/genetics,immunology,metabolism Cells, Cultured Cytokines/genetics,metabolism Dendritic Cells/drug effects,immunology,metabolism,pathology,virology Genetic Engineering Golgi Apparatus/drug effects,metabolism,virology Hydrogen-Ion Concentration/drug effects Ion Channels/genetics,immunology,metabolism Macrophages/drug effects,immunology,metabolism,pathology,virology Membrane Glycoproteins/genetics,immunology,metabolism Mice Mice, Inbred C57BL Mice, Knockout Monensin/pharmacology NLR Family, Pyrin Domain-Containing 3 Protein Oncogene Proteins, Viral/pharmacology Orthomyxoviridae/pathogenicity,physiology Orthomyxoviridae Infections/immunology,physiopathology Potassium Chloride/pharmacology Protein Transport/drug effects Protons Sequence Deletion/genetics Toll-Like Receptor 7/genetics,immunology,metabolism Viral Matrix Proteins/genetics,immunology,metabolism Virus Replication
Chemicals
Carrier Proteins Cytokines Ion Channels M2 protein, Influenza A virus Membrane Glycoproteins NLR Family, Pyrin Domain-Containing 3 Protein Nlrp3 protein, mouse Oncogene Proteins, Viral Protons Tlr7 protein, mouse Toll-Like Receptor 7 Viral Matrix Proteins oncogene protein E5, Bovine papillomavirus type 1 Potassium Chloride Monensin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Ichinohe Takeshi
Department of Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA.
Pang Iris K
Iwasaki Akiko
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1861
Published
2010-05-00
Epub
2010-00-11
Pages
404-10
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2857582
Subset
IM
Grants
NIAID NIH HHS · R01 AI064705-05 · United States
NIAID NIH HHS · AI083242 · United States
NIAID NIH HHS · AI064705 · United States
NIAID NIH HHS · R01 AI064705 · United States
NIAID NIH HHS · R21 AI083242-01 · United States
NIAID NIH HHS · R56 AI062428 · United States
NIAID NIH HHS · AI062428 · United States
NIAID NIH HHS · R01 AI062428 · United States
NIAID NIH HHS · R21 AI083242 · United States
External Links
PubMed source DOI: 10.1038/ni.1861 PMC Full Text View journal details
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