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  1. Article ; Online: Influenza virus activates inflammasomes via its intracellular M2 ion channel.

    Ichinohe, Takeshi / Pang, Iris K / Iwasaki, Akiko

    Nature immunology

    2010  Volume 11, Issue 5, Page(s) 404–410

    Abstract: ... M2 channel activity was required for the activation of inflammasomes by influenza and was sufficient ... a mechanism by which influenza virus infection activates inflammasomes and identify the sensing ... by which influenza virus activates the NLRP3 inflammasome is unknown. Here we show that the influenza virus M2 protein ...

    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 term(s) Animals ; Carrier Proteins/genetics ; Carrier Proteins/immunology ; Carrier Proteins/metabolism ; Cells, Cultured ; Cytokines/genetics ; Cytokines/metabolism ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Dendritic Cells/pathology ; Dendritic Cells/virology ; Genetic Engineering ; Golgi Apparatus/drug effects ; Golgi Apparatus/metabolism ; Golgi Apparatus/virology ; Hydrogen-Ion Concentration/drug effects ; Ion Channels/genetics ; Ion Channels/immunology ; Ion Channels/metabolism ; Macrophages/drug effects ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/pathology ; Macrophages/virology ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; Membrane Glycoproteins/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Monensin/pharmacology ; NLR Family, Pyrin Domain-Containing 3 Protein ; Oncogene Proteins, Viral/pharmacology ; Orthomyxoviridae/pathogenicity ; Orthomyxoviridae/physiology ; Orthomyxoviridae Infections/immunology ; Orthomyxoviridae Infections/physiopathology ; Potassium Chloride/pharmacology ; Protein Transport/drug effects ; Protons ; Sequence Deletion/genetics ; Toll-Like Receptor 7/genetics ; Toll-Like Receptor 7/immunology ; Toll-Like Receptor 7/metabolism ; Viral Matrix Proteins/genetics ; Viral Matrix Proteins/immunology ; Viral Matrix Proteins/metabolism ; Virus Replication
    Chemical Substances 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 (660YQ98I10) ; Monensin (906O0YJ6ZP)
    Language English
    Publishing date 2010-04-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/ni.1861
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Influenza Virus-Induced Oxidized DNA Activates Inflammasomes.

    Moriyama, Miyu / Nagai, Minami / Maruzuru, Yuhei / Koshiba, Takumi / Kawaguchi, Yasushi / Ichinohe, Takeshi

    iScience

    2020  Volume 23, Issue 7, Page(s) 101270

    Abstract: ... of influenza virus-induced oxidized DNA in inflammasomes activation. ... Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like receptor family ... by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus ...

    Abstract Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in macrophages by altering intracellular ionic balance or mitochondrial reactive oxygen species (ROS) production. However, the precise mechanism by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus stimulates oxidized DNA release from macrophages. Ion channel activity of the M2 protein or mitochondrial localization of the PB1-F2 protein was required for oxidized DNA release. The oxidized DNA enhanced influenza virus-induced IL-1β secretion, whereas inhibition of mitochondrial ROS production by antioxidant Mito-TEMPO decreased the virus-induced IL-1β secretion. In addition, we show that influenza virus stimulates IL-1β secretion from macrophages in an AIM2-dependent manner. These results provide a missing link between influenza viral proteins and the NLRP3 inflammasome activation and reveal the importance of influenza virus-induced oxidized DNA in inflammasomes activation.
    Keywords covid19
    Language English
    Publishing date 2020-06-14
    Publishing country United States
    Document type Journal Article
    ISSN 2589-0042
    ISSN (online) 2589-0042
    DOI 10.1016/j.isci.2020.101270
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Influenza Virus-Induced Oxidized DNA Activates Inflammasomes

    Miyu Moriyama / Minami Nagai / Yuhei Maruzuru / Takumi Koshiba / Yasushi Kawaguchi / Takeshi Ichinohe

    iScience, Vol 23, Iss 7, Pp 101270- (2020)

    2020  

    Abstract: ... of influenza virus-induced oxidized DNA in inflammasomes activation. ... Summary: Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like ... by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus ...

    Abstract Summary: Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in macrophages by altering intracellular ionic balance or mitochondrial reactive oxygen species (ROS) production. However, the precise mechanism by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus stimulates oxidized DNA release from macrophages. Ion channel activity of the M2 protein or mitochondrial localization of the PB1-F2 protein was required for oxidized DNA release. The oxidized DNA enhanced influenza virus-induced IL-1β secretion, whereas inhibition of mitochondrial ROS production by antioxidant Mito-TEMPO decreased the virus-induced IL-1β secretion. In addition, we show that influenza virus stimulates IL-1β secretion from macrophages in an AIM2-dependent manner. These results provide a missing link between influenza viral proteins and the NLRP3 inflammasome activation and reveal the importance of influenza virus-induced oxidized DNA in inflammasomes activation.
    Keywords Immunology ; Viral Microbiology ; Science ; Q
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Influenza virus-induced oxidized DNA activates inflammasomes

    Moriyama, Miyu / Nagai, Minami / Maruzuru, Yuhei / Koshiba, Takumi / Kawaguchi, Yasushi / Ichinohe, Takeshi

    iScience

    Abstract: ... of influenza virus-induced oxidized DNA in inflammasomes activation. ... Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like receptor family ... by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus ...

    Abstract Influenza virus M2 and PB1-F2 proteins have been proposed to activate the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome in macrophages by altering intracellular ionic balance or mitochondrial reactive oxygen species (ROS) production. However, the precise mechanism by which these viral proteins trigger the NLRP3 inflammasome activation remains unclear. Here we show that influenza virus stimulates oxidized DNA release from macrophages. Ion channel activity of the M2 protein or mitochondrial localization of the PB1-F2 protein was required for oxidized DNA release. While the oxidized DNA enhanced influenza virus-induced IL-1β secretion, inhibition of mitochondrial ROS production by antioxidant Mito-TEMPO decreased the virus-induced IL-1β secretion. In addition, we show that influenza virus stimulates IL-1β secretion from macrophages in an AIM2-dependent manner. These results provide a missing link between influenza viral proteins and the NLRP3 inflammaseome activation, and reveal the importance of influenza virus-induced oxidized DNA in inflammasomes activation.
    Keywords covid19
    Publisher PMC
    Document type Article ; Online
    DOI 10.1016/j.isci.2020.101270
    Database COVID19

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