Duck Enteritis Virus VP16 Antagonizes IFN-β-Mediated Antiviral Innate Immunity
Duck Enteritis Virus VP16 Antagonizes IFN-β-Mediated Antiviral Innate Immunity
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鸭肠炎病毒 VP16 拮抗 IFN-β 介导的抗病毒先天免疫
DOI：
10.1155/2020/9630452
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发表时间：
2020-05-16
影响因子：
4.1
通讯作者：
Chen, Xiaoyue
中科院分区：
文献类型：
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作者：
Li, Yang;Wang, Mingshu;Chen, Xiaoyue
鸭肠炎病毒（DEV）可以成功逃避宿主先天免疫反应，并在受感染宿主体内建立终生潜伏感染。然而，目前关于DEV如何逃避宿主先天免疫的研究仍然不足。在本研究中，我们首次鉴定了一种病毒蛋白VP16，DEV可以通过该蛋白明显下调鸭胚胎成纤维细胞（DEF）中IFN-β的产生。我们的结果表明，VP16 的异位表达降低了鸭 IFN-β (duIFN-β) 启动子的激活，并显着抑制 IFN-β mRNA 的转录。进一步的研究表明，VP16还可以明显抑制干扰素刺激基因（ISG）的mRNA转录，例如粘病毒抗性蛋白（Mx）和干扰素诱导的类寡聚腺苷酸合成酶（OASL）。此外，我们发现 VP16 的这种抗干扰素活性取决于其 N 末端 (aa1-200)。共表达分析显示，VP16 在 duIRF7 水平而非 duIRF1 选择性阻断 duIFN-β 启动子活性。根据共免疫沉淀分析（co-IP）和间接免疫荧光分析（IFA）的结果，VP16能够直接与鸭IRF7（duIRF7）结合，但在体外不与鸭IRF1（duIRF1）相互作用。
Duck enteritis virus (DEV) can successfully evade the host innate immune responses and establish a lifelong latent infection in the infected host. However, the study about how DEV escapes host innate immunity is still deficient up to now. In this study, for the first time, we identified a viral protein VP16 by which DEV can obviously downregulate the production of IFN-β in duck embryo fibroblast (DEF). Our results showed that ectopic expression of VP16 decreased duck IFN-β (duIFN-β) promoter activation and significantly inhibited the mRNA transcription of IFN-β. Further study showed that VP16 can also obviously inhibit the mRNA transcription of interferon-stimulated genes (ISGs), such as myxovirus resistance protein (Mx) and interferon-induced oligoadenylate synthetase-like (OASL). Furthermore, we found that this anti-interferon activity of VP16 depended on its N-terminus (aa1-200). Coexpression analysis revealed that VP16 selectively blocked duIFN-β promoter activity at the duIRF7 level rather than duIRF1. Based on the results of coimmunoprecipitation analysis (co-IP) and indirect immunofluorescence assay (IFA), VP16 was able to bind to duck IRF7 (duIRF7) directly, but did not interact with duck IRF1 (duIRF1) in vitro.