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  1. Artikel ; Online: The inflammasome pathway is activated by dengue virus non-structural protein 1 and is protective during dengue virus infection.

    Wong, Marcus P / Juan, Evan Y W / Pahmeier, Felix / Chelluri, Sai S / Wang, Phoebe / Castillo-Rojas, Bryan / Blanc, Sophie F / Biering, Scott B / Vance, Russell E / Harris, Eva

    PLoS pathogens

    2024  Band 20, Heft 4, Seite(n) e1012167

    Abstract: Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a ... ...

    Abstract Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1β in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1β. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection.
    Mesh-Begriff(e) Viral Nonstructural Proteins/metabolism ; Viral Nonstructural Proteins/immunology ; Animals ; Inflammasomes/metabolism ; Inflammasomes/immunology ; Dengue/immunology ; Dengue/virology ; Dengue/metabolism ; Mice ; Dengue Virus/immunology ; Humans ; Macrophages/immunology ; Macrophages/metabolism ; Macrophages/virology ; Interleukin-1beta/metabolism ; Interleukin-1beta/immunology ; Mice, Inbred C57BL ; Mice, Knockout ; Caspase 1/metabolism
    Chemische Substanzen Viral Nonstructural Proteins ; Inflammasomes ; Interleukin-1beta ; Caspase 1 (EC 3.4.22.36) ; NS1 protein, dengue-1 virus
    Sprache Englisch
    Erscheinungsdatum 2024-04-25
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1012167
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel: The Inflammasome Pathway is Activated by Dengue Virus Non-structural Protein 1 and is Protective During Dengue Virus Infection.

    Wong, Marcus P / Juan, Evan Y W / Chelluri, Sai S / Wang, Phoebe / Pahmeier, Felix / Castillo-Rojas, Bryan / Blanc, Sophie F / Biering, Scott B / Vance, Russell E / Harris, Eva

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a ... ...

    Abstract Dengue virus (DENV) is a medically important flavivirus causing an estimated 50-100 million dengue cases annually, some of whom progress to severe disease. DENV non-structural protein 1 (NS1) is secreted from infected cells and has been implicated as a major driver of dengue pathogenesis by inducing endothelial barrier dysfunction. However, less is known about how DENV NS1 interacts with immune cells and what role these interactions play. Here we report that DENV NS1 can trigger activation of inflammasomes, a family of cytosolic innate immune sensors that respond to infectious and noxious stimuli, in mouse and human macrophages. DENV NS1 induces the release of IL-1β in a caspase-1 dependent manner. Additionally, we find that DENV NS1-induced inflammasome activation is independent of the NLRP3, Pyrin, and AIM2 inflammasome pathways, but requires CD14. Intriguingly, DENV NS1-induced inflammasome activation does not induce pyroptosis and rapid cell death; instead, macrophages maintain cellular viability while releasing IL-1β. Lastly, we show that caspase-1/11-deficient, but not NLRP3-deficient, mice are more susceptible to lethal DENV infection. Together, these results indicate that the inflammasome pathway acts as a sensor of DENV NS1 and plays a protective role during infection.
    Sprache Englisch
    Erscheinungsdatum 2023-09-21
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.1101/2023.09.21.558875
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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