國家衛生研究院 NHRI:Item 3990099045/1669
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/1669


    Title: Dengue virus type 2 antagonizes IFN-alpha but not IFN-gamma antiviral effect via down-regulating Tyk2-STAT signaling in the human dendritic cell
    Authors: Ho, LJ;Hung, LF;Weng, CY;Wu, WL;Chou, P;Lin, YL;Chang, DM;Tai, TY;Lai, JH
    Contributors: Division of Gerontology Research
    Abstract: The immunopathogenesis mechanism of dengue virus (DV) infection remains elusive. We previously showed that the target of DV in humans is dendritic cells (DCs), the primary sentinels of immune system. We also observed that despite the significant amount of IFN-alpha induced; DV particles remain massively produced from infected DCs. It suggests that DV may antagonize the antiviral effect of IFN-alpha. Recent work in animal studies demonstrated the differential critical roles of antiviral cytokines, namely IFN-alpha/IFN-beta and IFN-gamma, in blocking early viral production and in preventing viral-mediated disease, respectively. In this study, we examined the effects of IFN-alpha and IFN-gamma in DV infection of monocyte-derived DCs. We showed that the preinfection treatment with either IFN-alpha or IFN-gamma effectively armed DCs and limited viral production in infected cells. However, after infection, DV developed mechanisms to counteract the protection from lately added IFN-alpha, but not IFN-gamma. Such a selective antagonism on antiviral effect of IFN-alpha, but not IFN-gamma, correlated with down-regulated tyrosine-phosphorylation and DNA-binding activities of STAT1 and STAT3 transcription factors by DV. Furthermore, subsequent studies into the underlying mechanisms revealed that DV attenuated IFN-alpha-induced tyrosine-phosphorylation of Tyk2, an upstream molecule of STAT activation, but had no effect on expression of both IFN-alpha receptor 1 and IFN-a receptor 2. Moreover, DV infection by itself could activate STAT1 and STAT3 through IFN-alpha-dependent and both IFN-alpha-dependent and IFN-alpha-independent mechanisms, respectively. These observations provide very useful messages with physiological significance in investigation of the pathogenesis, the defense mechanisms of human hosts and the therapeutic considerations in DV infection.
    Keywords: Immunology
    Date: 2005-06-15
    Relation: Journal of Immunology. 2005 Jun;174(12):8163-8172.
    Link to: http://www.jimmunol.org/cgi/content/abstract/174/12/8163
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0022-1767&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000229791400083
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=20444409731
    Appears in Collections:[Tong-Yuan Tai(2003-2005)] Periodical Articles
    [Ling-Jun Ho] Periodical Articles

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