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.

干扰素调节因子 (IRF) 是参与 I 型干扰素 (IFN) 和 IFN 刺激基因 (ISG) 针对病毒感染的转录调节的关键转录因子。在硬骨鱼中，已经发现了 11 个 IRF，然而，对其在抗病毒反应中的作用的了解仍然有限。在之前的研究中，IRF1（Lc IRF1）和IRF2（Lc IRF2）基因是从大黄鱼（Larimichthys crocea）中克隆出来的。在这里，我们进一步描述了它们在抗病毒反应中的功能。Lc IRF1 和LcIRF2 在原代头肾单核细胞/巨噬细胞 (PKMs)、淋巴细胞 (PKLs)、粒细胞 (PKGs) 和大黄鱼头肾 (LYCK) 细胞系中组成型表达，并且在用 poly (I) 刺激后在 PKMs 和 LYCK 细胞中显着上调：C）。Lc IRF1可以诱导三种大黄鱼I型干扰素IFNc、IFNd和IFNh的启动子活性，而Lc IRF2只能诱导IFNd和IFNh的启动子活性，并抑制IFNc启动子活性。相应地，LYCK 细胞中Lc IRF1 的过表达增加了所有三种 IFN（IFNc、IFNd 和 IFNh）的表达，而Lc IRF2 仅上调了 IFNd 和 IFNh 的表达水平，并抑制了 IFNc 的表达，尽管两种LcIRF1 和Lc IRF2 诱导 IFN 刺激基因 (ISG)、MxA、PKR 和 Viperin 的表达。此外，Lc IRF1和Lc IRF2 均能抑制鲤鱼上皮瘤 (EPC) 细胞中的鲤春病毒血症 (SVCV) 复制，从而显示出抗病毒活性。总之，这些结果表明Lc IRF1和Lc IRF2均通过诱导不同的I型干扰素亚群在调节大黄鱼的抗病毒反应中发挥积极作用。