Dengue Virus Subverts the Interferon Induction Pathway via NS2B/3 Protease-IκB Kinase e Interaction
Dengue Virus Subverts the Interferon Induction Pathway via NS2B/3 Protease-IκB Kinase e Interaction
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DOI：
10.1128/cvi.00500-13
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Sariol, Carlos A.
中科院分区：
文献类型：
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作者：
Anglero-Rodriguez, Yesseinia I.;Pantoja, Petraleigh;Sariol, Carlos A.
登革热是世界上最常见的蚊媒病毒感染，也是整个热带和亚热带地区发病的主要原因。已知病毒通过调节干扰素调节因子3（IRF 3）的活化来逃避抗病毒状态的建立，所述干扰素调节因子3是α/β干扰素诱导途径中的关键转录因子。在这里，我们表明，登革病毒（DENV）绕过诱导的维甲酸诱导基因I样受体（RLR）途径在感染过程中通过阻断丝氨酸386磷酸化和核转位的IRF 3。这种效应与人细胞中非结构2B/3蛋白（NS 2B/3）蛋白酶的表达有关。利用相互作用分析，我们发现NS 2 B/3与细胞I κ B激酶A（IKK A）相互作用。对接计算分析显示，在这种相互作用中，NS 2 B/3掩盖了IKK β的激酶结构域，并可能影响其功能。这一观察结果得到了DENV相关的IKK β激酶活性抑制的支持。我们的数据确定IKK β是DENV NS 2B/3蛋白酶的新靶标。
Dengue is the world's most common mosquito-borne viral infection and a leading cause of morbidity throughout the tropics and subtropics. Viruses are known to evade the establishment of an antiviral state by regulating the activation of interferon regulatory factor 3 (IRF3), a critical transcription factor in the alpha/beta interferon induction pathway. Here, we show that dengue virus (DENV) circumvents the induction of the retinoic acid-inducible gene I-like receptor (RLR) pathway during infection by blocking serine 386 phosphorylation and nuclear translocation of IRF3. This effect is associated with the expression of nonstructural 2B/3 protein (NS2B/3) protease in human cells. Using interaction assays, we found that NS2B/3 interacts with the cellular I kappa B kinase epsilon (IKK epsilon). Docking computational analysis revealed that in this interaction, NS2B/3 masks the kinase domain of IKK epsilon and potentially affects its functionality. This observation is supported by the DENV-associated inhibition of the kinase activity of IKK epsilon. Our data identify IKK epsilon as a novel target of DENV NS2B/3 protease.