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  1. Article ; Online: The Role of Non-Structural Protein NSs in the Pathogenesis of Severe Fever with Thrombocytopenia Syndrome.

    Khalil, Jumana / Kato, Hiroki / Fujita, Takashi

    Viruses

    2021  Volume 13, Issue 5

    Abstract: Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating viral pathogenesis and disease progression through various mechanisms. NSs has been ... ...

    Abstract Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating viral pathogenesis and disease progression through various mechanisms. NSs has been described as a potent interferon antagonist and NF-κB agonist, two divergent signaling pathways in many immune responses upon a viral encounter. In this review, we highlight the many mechanisms used by NSs on the host that promote viral replication and hyper-inflammation. Understanding these host-pathogen interactions is crucial for antiviral therapy development.
    MeSH term(s) Animals ; Biomarkers ; Cytokine Release Syndrome/etiology ; Cytokine Release Syndrome/metabolism ; Cytokines/metabolism ; Disease Models, Animal ; Disease Susceptibility ; Host-Pathogen Interactions ; Humans ; Phlebovirus/physiology ; Severe Fever with Thrombocytopenia Syndrome/complications ; Severe Fever with Thrombocytopenia Syndrome/etiology ; Severe Fever with Thrombocytopenia Syndrome/metabolism ; Viral Nonstructural Proteins/metabolism ; Virus Replication
    Chemical Substances Biomarkers ; Cytokines ; Viral Nonstructural Proteins
    Language English
    Publishing date 2021-05-11
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13050876
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: The Role of Non-Structural Protein NSs in the Pathogenesis of Severe Fever with Thrombocytopenia Syndrome

    Khalil, Jumana / Kato, Hiroki / Fujita, Takashi

    Viruses. 2021 May 11, v. 13, no. 5

    2021  

    Abstract: Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating viral pathogenesis and disease progression through various mechanisms. NSs has been ... ...

    Abstract Viral non-structural proteins, such as NSs of the newly emerging severe fever with thrombocytopenia syndrome virus, are well established virulence factors, mediating viral pathogenesis and disease progression through various mechanisms. NSs has been described as a potent interferon antagonist and NF-κB agonist, two divergent signaling pathways in many immune responses upon a viral encounter. In this review, we highlight the many mechanisms used by NSs on the host that promote viral replication and hyper-inflammation. Understanding these host-pathogen interactions is crucial for antiviral therapy development.
    Keywords Huaiyangshan banyangvirus ; agonists ; antagonists ; disease progression ; interferons ; pathogenesis ; severe fever with thrombocytopenia syndrome ; therapeutics ; viral nonstructural proteins ; virulence ; virus replication
    Language English
    Dates of publication 2021-0511
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-AP-2-clean
    ZDB-ID 2516098-9
    ISSN 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v13050876
    Database NAL-Catalogue (AGRICOLA)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  3. Article ; Online: The Nonstructural Protein NSs of Severe Fever with Thrombocytopenia Syndrome Virus Causes a Cytokine Storm through the Hyperactivation of NF-κB

    Khalil, Jumana / Yamada, Shintarō / Tsukamoto, Yuta / Abe, Hiroto / Shimojima, Masayuki / Kato, Hiroki / Fujita, Takashi

    Molecular and Cellular Biology. 2021 Mar. 1, v. 41, no. 3 p.e00542-20-

    2021  

    Abstract: Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging highly pathogenic phlebovirus. The syndrome is characterized by the substantial production of inflammatory cytokines and chemokines, described as a cytokine storm, which ... ...

    Abstract Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging highly pathogenic phlebovirus. The syndrome is characterized by the substantial production of inflammatory cytokines and chemokines, described as a cytokine storm, which correlates with multiorgan failure and high mortality. SFSTV nonstructural (NSs) protein was suggested to mediate the pathogenesis by inhibiting antiviral interferon signaling in the host. However, whether SFTSV NSs protein mediates the induction of a fatal cytokine storm remains unaddressed. We demonstrated that SFTSV NSs promotes the hyperinduction of cytokine/chemokine genes in vitro, reminiscent of a cytokine storm. Using gene deletion and pharmacological intervention, we found that the induced cytokine storm is driven by the transcription factor NF-κB. Our investigation revealed that TANK-binding kinase 1 (TBK1) suppresses NF-κB signaling and cytokine/chemokine induction in a kinase activity-dependent manner and that NSs sequesters TBK1 to prevent it from suppressing NF-κB, thereby promoting the activation of NF-κB and its target cytokine/chemokine genes. Of note, NF-κB inhibition suppressed the induction of proinflammatory cytokines in SFTSV-infected type I interferon (IFN-I) receptor 1-deficient (Ifnar1⁻/⁻) mice. These findings establish the essential role of NSs in SFTS pathogenesis and suggest NF-κB as a possible therapeutic target.
    Keywords Huaiyangshan banyangvirus ; Phlebovirus ; cell biology ; chemokines ; gene deletion ; interferons ; mortality ; pathogenesis ; severe fever with thrombocytopenia syndrome ; therapeutics ; transcription factors ; viral nonstructural proteins ; viruses ; SFTSV NSs ; NF-κB ; cytokine storm ; TBK1 ; viral pathogenesis
    Language English
    Dates of publication 2021-0301
    Publishing place Taylor & Francis
    Document type Article ; Online
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.00542-20
    Database NAL-Catalogue (AGRICOLA)

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    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1666: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

  4. Article ; Online: The Non-structural Protein NSs of SFTSV Causes Cytokine Storm Through the Hyper-activation of NF-κB.

    Khalil, Jumana / Yamada, Shintaro / Tsukamoto, Yuta / Abe, Hiroto / Shimojima, Masayuki / Kato, Hiroki / Fujita, Takashi

    Molecular and cellular biology

    2020  

    Abstract: Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging highly pathogenic phlebovirus. The syndrome is characterized by the substantial production of inflammatory cytokines and chemokines, described as cytokine storm, which ... ...

    Abstract Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging highly pathogenic phlebovirus. The syndrome is characterized by the substantial production of inflammatory cytokines and chemokines, described as cytokine storm, which correlates with multi-organ failure and high mortality. SFSTV nonstructural (NSs) protein was suggested to mediate the pathogenesis by inhibiting antiviral interferon signaling in the host. However, whether SFTSV NSs protein mediates the induction of fatal cytokine storm remains unaddressed. We demonstrated that SFTSV NSs promotes the hyper-induction of cytokine/chemokine genes
    Language English
    Publishing date 2020-12-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 779397-2
    ISSN 1098-5549 ; 0270-7306
    ISSN (online) 1098-5549
    ISSN 0270-7306
    DOI 10.1128/MCB.00542-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

    More links

    Kategorien

    In stock of ZB MED Cologne/Königswinter

    Zs.A 1666: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Order via subito

    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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