A novel short transcript isoform of chicken IRF7 negatively regulates interferon-β production
A novel short transcript isoform of chicken IRF7 negatively regulates interferon-β production
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DOI：
10.1016/j.jia.2022.12.015
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发表时间：
2023-07-21
影响因子：
4.8
通讯作者：
Wang，Zeng
中科院分区：
文献类型：
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作者：
Ma，Yu-chen;Chen，Hua-yuan;Wang，Zeng
I型干扰素（IFN-1）是保护鸟类免受病原体入侵的重要第一线药物。IFN调节因子7（IRF 7）是DNA和RNA病毒诱导鸡产生IFN-Ⅰ的最重要的调节因子。尽管在哺乳动物中已经鉴定出IRF 7的四种剪接变体，但仍不清楚IRF 7同种型是否存在于鸡中的选择性剪接模式和功能。在这项研究中，我们报道了一种新的短转录本亚型鸡IRF 7（chIRF 7），称为chIRF 7-iso，它包含一个完整的N端DNA结合结构域（DBD）和14个氨基酸不同于chIRF 7的C端。chIRF 7在鸡来航雄性肝细胞（LMH）中的过表达激活IFN-β启动子并显著抑制纽卡斯尔病毒（NDV）和禽腺病毒血清4型（FAdV-4）的复制。相反，chIRF 7-iso的过表达阻断了IFN-β启动子的活性，并有利于NDV和FAdV-4的体外复制。总的来说，我们的结果证实了一种新的chIRF 7亚型介导的负调控IFN-β的产生，这将有助于理解chIRF 7在鸡先天性抗病毒反应中的作用。
Type I interferon (IFN-I) provides an important first line to protect avian species against pathogens invasion. IFN regulatory factor 7 (IRF7) has been identified as the most important regulator for both DNA and RNA virus-induced IFN-I production in chickens. Although four splicing variants of IRF7 have been identified in mammals, it is still unclear whether alternative splicing patterns and the function of IRF7 isoform(s) exist in chickens. In this study, we reported a novel short transcript isoform of chicken IRF7 (chIRF7), termed chIRF7-iso, which contained an intact N-terminal DNA-binding domain (DBD) and 14 amino acids different from chIRF7 in the C-terminal. Overexpression of chIRF7 in chicken leghorn male hepatocellular (LMH) cells activated the IFN-β promoter and significantly inhibited Newcastle disease virus (NDV) and fowl adenovirus serotype 4 (FAdV-4) replication. Conversely, overexpression of chIRF7-iso blocked the IFN-β promoter activity and was favorable for NDV and FAdV-4 replicationin vitro. Collectively, our results confirm that a novel chIRF7 isoform-mediated negative regulates IFN-β production, which will contribute to understanding the role of chIRF7 in innate antiviral response in chicken.