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. (May 2021)

• Record Type: Journal Article
• Authors: Chen, Xiaojuan; Guan, Yanyun; Li, Kexin; Luo, Tian; Mu, Yinnan; Chen, Xinhua
• Is Part Of: Developmental and comparative immunology. Volume 118(2021)
• Publication Date: 2021-05
• Subjects: Large yellow croaker (Larimichthys crocea) -- IFR1 -- IRF2 -- Type I IFNs -- Antiviral response; Immunology -- Periodicals; Developmental immunology -- Periodicals; 616.079
• DOI: 10.1016/j.dci.2021.103996
• Languages: English
• ISSNs: 0145-305X

Abstract

Abstract: 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 ( Lc IRF1) and IRF2 ( Lc IRF2) genes were cloned from large yellow croaker ( Larimichthys crocea ). Here, we further characterized their function in the antiviral response. Lc IRF1 and Lc IRF2 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). Lc IRF1 could induce promoter activities of three large yellow croaker type I IFNs, IFNc, IFNd and IFNh, while Lc IRF2 could only induce those of IFNd and IFNh, and inhibit IFNc promoter activity. Correspondingly, overexpression of Lc IRF1 in LYCK cells increased expression of all three IFNs (IFNc, IFNd and IFNh), while that of Lc IRF2 only upregulated the expression levels of IFNd and IFNh, and inhibited expression of IFNc, although both Lc IRF1and Lc IRF2 induced expression of IFN-stimulated genes (ISGs), MxA, PKR and Viperin. Additionally, both Lc IRF1 and Lc IRF2 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 Lc IRF1 and Lc IRF2 play positive roles in regulating the antiviral response of large yellow croaker by induction of distinct subgroups of type I IFNs. Highlights: Lc IRF1 and Lc IRF2 were constitutively expressed in immune cells, and upregulated in PKMs and LYCK cells by poly (I:C). Lc IRF1 and Lc IRF2 differentially activated promoter activities of type I IFNs. Lc IRF1 upregulated expression of large yellow croaker IFNc, IFNd and IFNh, but Lc IRF2 inhibited IFNc expression. Overexpression of both Lc IRF1 and Lc IRF2 inhibited SVCV replication in EPC cells.