Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-κB activation
Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-κB activation
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DOI：
10.1016/j.micinf.2005.06.014
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发表时间：
2006-01-01
影响因子：
5.8
通讯作者：
Lin, YL
中科院分区：
文献类型：
--
作者：
Chang, TH;Liao, CL;Lin, YL
在这项研究中，我们发现感染黄病毒，如日本脑炎病毒（JEV）和登革热病毒血清2型（DEN-2），导致干扰素- β (ifn - β)基因以病毒复制和新生蛋白合成依赖的方式表达。NF-kappa B的激活对于JEV和den -2感染细胞中ifn - β的诱导至关重要。然而，这两种病毒似乎优先针对干扰素调节因子（IRF）家族的不同成员。组成性表达的IRF-3的激活，以较慢的凝胶迁移、二聚体形成和核易位为特征，在jev感染的细胞中更为明显。IRF家族的其他成员，如IRF-1和IRF-7也可由DEN-2诱导，但不受乙脑病毒感染的影响。进一步研究了IRF-3和NF-kappa B活化的上游分子。显然，细胞RNA解旋酶，视黄酸诱导基因I （RIG-I）和细胞激酶，磷脂酰肌醇-3激酶（PI3K），分别是黄病毒诱导的IRF-3和nf - κ B激活所必需的。因此，我们认为乙脑病毒和DEN-2通过涉及rig - 1 /IRF-3和PI3K/NF-kappa B信号通路的分子机制启动宿主先天免疫应答。(c) 2005 Elsevier SAS。版权所有。
In this study, we found that infection with flaviviruses, such as Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2), leads to interferon-beta (IFN-beta) gene expression in a virus-replication- and de novo protein-synthesis-dependent manner. NF-kappa B activation is essential for IFN-beta induction in JEV- and DEN-2-infected cells. However, these two viruses seem to preferentially target different members of the interferon regulatory factor (IRF) family. The activation of constitutively expressed IRF-3, characterized by slower gel mobility, dimer formation, and nuclear translocation, is more evident in JEV-infected cells. Other members of the IRF family, such as IRF-1 and IRF-7 are also induced by DEN-2, but not by JEV infection. The upstream molecules responsible for IRF-3 and NF-kappa B activation were further studied. Evidently, a cellular RNA helicase, retinoic acid-inducible gene I (RIG-I), and a cellular kinase, phosphatidylinositol-3 kinase (PI3K), are required for flavivirus-induced IRF-3 and NF-kappa B activation, respectively. Therefore, we suggest that JEV and DEN-2 initiate the host innate immune response through a molecular mechanism involving RIG-I/IRF-3 and PI3K/NF-kappa B signaling pathways. (c) 2005 Elsevier SAS. All rights reserved.