Duck Tembusu Virus Nonstructural Protein 1 Antagonizes IFN-β Signaling Pathways by Targeting VISA
Duck Tembusu Virus Nonstructural Protein 1 Antagonizes IFN-β Signaling Pathways by Targeting VISA
复制标题
鸭天宝苏病毒非结构蛋白 1 通过靶向 VISA 拮抗 IFN-β 信号通路
DOI：
10.4049/jimmunol.1502317
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发表时间：
2016-12-15
影响因子：
4.4
通讯作者：
Zhu, Qiyun
中科院分区：
文献类型：
--
作者：
Wang, Junyong;Lei, Cao-Qi;Zhu, Qiyun
鸭坦布苏病毒（DuckTembusuvirus，DTMUV）是2009年以来在我国暴发流行的一种鸭传染病，给我国养禽业造成了巨大的经济损失。以前，我们表明DTMUV抑制IFN-β诱导早期感染，然而，先天免疫反应的抑制机制仍然知之甚少。在这项研究中，我们筛选DTMUV编码的结构和非结构蛋白，使用报告分析，发现DTMUV NS 1显着抑制病毒触发的IFN-β的表达，通过抑制视黄酸诱导的基因I样受体信号。此外，我们发现DTMUV NS 1特异性地与病毒诱导的信号衔接子的C端结构域相互作用，并破坏视黄酸诱导基因I或黑素瘤分化相关基因5与病毒诱导的信号衔接子的结合，从而下调视黄酸诱导基因I样受体介导的信号转导和细胞抗病毒反应，导致先天免疫应答的逃避。总之，我们的研究结果揭示了DTMUV操纵的一种新机制，以规避宿主的抗病毒免疫反应。
Duck Tembusu virus (DTMUV) is an emergent infectious pathogen that has caused severe disease in ducks and huge economic losses to the poultry industry in China since 2009. Previously, we showed that DTMUV inhibits IFN-beta induction early in infection; however, the mechanisms of the inhibition of innate immune responses remain poorly understood. In this study, we screened DTMUV-encoded structural and nonstructural proteins using reporter assays and found that DTMUV NS1 markedly suppressed virus-triggered IFN-beta expression by inhibiting retinoic acid-inducible gene I-like receptor signaling. Moreover, we found that DTMUV NS1 specifically interacted with the C-terminal domain of virus-induced signaling adaptor and impaired the association of retinoic acid-inducible gene I or melanoma differentiation-associated gene 5 and virus-induced signaling adaptor, thereby downregulating the retinoic acid-inducible gene I-like receptor-mediated signal transduction and cellular antiviral responses, leading to evasion of the innate immune response. Together, our findings reveal a novel mechanism manipulated by DTMUV to circumvent the host antiviral immune response.