IRF1 and IRF2 act as positive regulators in antiviral response of large yellow croaker (Larimichthys crocea) by induction of distinct subgroups of type I IFNs
IRF1 and IRF2 act as positive regulators in antiviral response of large yellow croaker (Larimichthys crocea) by induction of distinct subgroups of type I IFNs
复制标题
IRF1 和 IRF2 通过诱导 I 型 IFN 的不同亚群，在大黄鱼 (Larimichthys crocea) 的抗病毒反应中发挥正调节作用。
DOI：
10.1016/j.dci.2021.103996
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发表时间：
2021-01-15
影响因子：
2.9
通讯作者：
Chen, Xinhua
中科院分区：
文献类型：
--
作者：
Chen, Xiaojuan;Guan, Yanyun;Chen, Xinhua
干扰素调节因子（Interferon Regulatory Factor，IRFs）是参与I型干扰素（Type I interferon，IFN）和IFN刺激基因（Interferon-stimulated genes，ISGs）抗病毒转录调控的重要转录因子。在硬骨鱼中，已发现11个IRF，然而，对其在抗病毒反应中的作用的了解仍然有限。在前期的研究中，从大黄鱼（Larimichthys crocea）中克隆了IRF 1（LcIRF 1）和IRF 2（LcIRF 2）基因。在这里，我们进一步表征了它们在抗病毒反应中的功能。LcIRF 1和LcIRF 2在原代头肾单核/巨噬细胞（PKM）、淋巴细胞（PKL）、粒细胞（PKG）和大黄鱼头肾（LYCK）细胞系中呈组成型表达，经poly（I：C）刺激后，PKM和LYCK细胞中LcIRF 1和LcIRF 2的表达显著上调。LcIRF 1能诱导大黄鱼I型IFN-γ、IFN-γ和IFN-γ h的启动子活性，而LcIRF 2仅能诱导IFN-γ和IFN-γ h的启动子活性，并抑制IFN-γ的启动子活性。相应地，LcIRF 1在LYCK细胞中的过表达增加了所有三种IFN（IFNc，IFNd和IFNh）的表达，而LcIRF 2仅上调IFNd和IFNh的表达水平，并抑制IFNc的表达，尽管LcIRF 1和LcIRF 2都诱导了IFN刺激基因（ISGs）MxA，PKR和Viperin的表达。此外，LcIRF 1和LcIRF 2都抑制鲤鱼春季病毒血症病毒（SVCV）在上皮瘤丘疹鲤（EPC）细胞中的复制，从而显示出抗病毒活性。综上所述，这些结果表明LcIRF 1和LcIRF 2通过诱导不同的I型干扰素亚群来调节大黄鱼的抗病毒反应，发挥积极作用。
Interferon regulatory factors (IRFs) are crucial transcription factors involved in transcriptional regulation of type I interferons (IFNs) and IFN-stimulated genes (ISGs) against viral infection. In teleost fish, eleven IRFs have been found, however, understanding of their roles in the antiviral response remains limited. In the previous study, IRF1 (LcIRF1) and IRF2 (LcIRF2) genes were cloned from large yellow croaker (Larimichthys crocea). Here, we further characterized their function in the antiviral response. LcIRF1 and LcIRF2 were constitutively expressed in primary head kidney monocytes/macrophages (PKMs), lymphocytes (PKLs), granulocytes (PKGs) and large yellow croaker head kidney (LYCK) cell line, and significantly upregulated in PKMs and LYCK cells after stimulation with poly (I:C). LcIRF1 could induce promoter activities of three large yellow croaker type I IFNs, IFNc, IFNd and IFNh, while LcIRF2 could only induce those of IFNd and IFNh, and inhibit IFNc promoter activity. Correspondingly, overexpression of LcIRF1 in LYCK cells increased expression of all three IFNs (IFNc, IFNd and IFNh), while that of LcIRF2 only upregulated the expression levels of IFNd and IFNh, and inhibited expression of IFNc, although both LcIRF1and LcIRF2 induced expression of IFN-stimulated genes (ISGs), MxA, PKR and Viperin. Additionally, both LcIRF1 and LcIRF2 inhibited the Spring Viremia of Carp Virus (SVCV) replication in epithelioma papulosum cyprinid (EPC) cells, thus showing antiviral activity. Taken together, these results indicated that both LcIRF1 and LcIRF2 play positive roles in regulating the antiviral response of large yellow croaker by induction of distinct subgroups of type I IFNs.