國家衛生研究院 NHRI:Item 3990099045/14922
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    题名: Negative regulation of type I interferon signaling by integrin-linked kinase permits dengue virus replication
    作者: Kao, YS;Wang, LC;Chang, PC;Lin, HM;Lin, YS;Yu, CY;Chen, CC;Lin, CF;Yeh, TM;Wan, SW;Wang, JR;Ho, TS;Chu, CC;Zhang, BC;Chang, CP
    贡献者: National Institute of Infectious Diseases and Vaccinology
    摘要: Dengue virus (DENV) infection can induce life-threatening dengue hemorrhagic fever/dengue shock syndrome in infected patients. DENV is a threat to global health due to its growing numbers and incidence of infection in the last 50 years. During infection, DENV expresses ten structural and nonstructural proteins modulating cell responses to benefit viral replication. However, the lack of knowledge regarding the cellular proteins and their functions in enhancing DENV pathogenesis impedes the development of antiviral drugs and therapies against fatal DENV infection. Here, we identified that integrin-linked kinase (ILK) is a novel enhancing factor for DENV infection by suppressing type I interferon (IFN) responses. Mechanistically, ILK binds DENV NS1 and NS3, activates Akt and Erk, and induces NF-κB-driven suppressor of cytokine signaling 3 (SOCS3) expression. Elevated SOCS3 in DENV-infected cells inhibits phosphorylation of STAT1/2 and expression of interferon-stimulated genes (ISGs). Inhibiting ILK, Akt, or Erk activation abrogates SOCS3 expression. In DENV-infected mice, the treatment of an ILK inhibitor significantly reduces viral loads in the brains, disease severity, and mortality rate. Collectively, our results show that ILK is a potential therapeutic target against DENV infection.
    日期: 2023-03-17
    關聯: PLOS Pathogens. 2023 Mar 17;19(3):Article number e1011241.
    Link to: http://dx.doi.org/10.1371/journal.ppat.1011241
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1553-7366&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000953294600001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85151312771
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