Broad-spectrum antiviral functions of duck interferon-induced protein with tetratricopeptide repeats (AvIFIT)
Broad-spectrum antiviral functions of duck interferon-induced protein with tetratricopeptide repeats (AvIFIT)
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鸭干扰素诱导的四肽重复蛋白 (AvIFIT) 的广谱抗病毒功能
DOI：
10.1016/j.dci.2018.02.007
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发表时间：
2018-07-01
影响因子：
2.9
通讯作者：
Huang, Yinhua
中科院分区：
文献类型：
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作者：
Rong, Enguang;Hu, Jiaxiang;Huang, Yinhua
哺乳动物干扰素诱导的三肽重复序列蛋白（IFIT）在许多细胞过程和宿主对病毒的天然免疫应答中起着重要作用。然而，IFIT蛋白在鸟类中的功能在很大程度上是未知的。在这里，我们首先描述了唯一一个鸟类IFIT蛋白是直系同源于哺乳动物IFIT的祖先。我们发现鸭AvIFIT蛋白的预测结构与人IFIT 5的结构相似。我们还发现，鸭AvIFIT蛋白显示出抗病毒活性，以广泛的特定的RNA和DNA病毒像哺乳动物IFIT蛋白。进一步的分析表明，鸭AvIFIT蛋白在DF 1细胞中的过表达导致与生长停滞相关的G1/S转换的细胞的显著积累，并且可能促进凋亡。此外，鸭AvIFIT结合H5 N1流感病毒的核蛋白（NP），并上调DF 1细胞中涉及IFN途径的基因的表达。综上所述，我们的研究结果支持鸭AvIFIT蛋白通过影响病毒NP蛋白的功能、放大IFN信号传导和抑制细胞生长在宿主对病毒（至少是H5 N1病毒）的免疫应答中起关键作用。(C)2018爱思唯尔有限公司版权所有
Mammalian interferon-induced proteins with tetratricopeptide repeats (IFITs) play important roles in many cellular processes and host innate immune response to viruses. However, the functions of IFIT proteins in birds are largely unknown. Here, we first describe that the only one avian IFIT protein is orthologous to ancestor of mammalian IFITs. We find that the predicted structure of duck AvIFIT protein is similar to that of human IFIT5. We also find that duck AvIFIT protein shows antiviral activity to a broad range of specific RNA and DNA viruses like mammalian IFIT proteins. Further analysis indicates that overexpression of duck AvIFIT protein in DF1 cells leads to a remarkable accumulation of cells at G1/S transition associated with growth arrest and may promote apoptosis. Moreover, duck AvIFIT binds to nucleoprotein (NP) of H5N1 influenza virus and upregulates the expression of genes involving the IFN pathway in DF1 cells. In summary, our findings support that duck AvIFIT protein plays critical role in host immune response to viruses, at least H5N1 virus, through affecting function of viral NP protein, magnifying the IFN signaling and arresting cell growth. (C) 2018 Elsevier Ltd. All rights reserved.