Zebrafish Ism1 is a novel antiviral factor that positively regulates antiviral immune responses
Zebrafish Ism1 is a novel antiviral factor that positively regulates antiviral immune responses
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DOI：
10.1016/j.dci.2021.104210
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发表时间：
2021-07-29
影响因子：
2.9
通讯作者：
Ji, Guangdong
中科院分区：
文献类型：
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作者：
Li, Congjun;Zhong, Shenjie;Ji, Guangdong
Isthmin 1（Ism 1），2002年首次被鉴定为非洲爪蟾胚胎中的分泌蛋白，已被证明具有多种生物学功能，但目前对其在免疫中的作用知之甚少。在这里，我们表明，表达ism/诱导的挑战与草鱼呼肠孤病毒（GCRV）在斑马鱼，这表明Ism 1参与抗病毒反应。结果表明，重组Ism 1（rIsm 1）能降低GCRV感染细胞的致细胞病变效应，促进I型IFN基因和IFN诱导的抗病毒蛋白Mxa基因的表达，降低病毒感染细胞和宿主体内的病毒量。rIsm 1能促进tbk 1、irf 3和irf 7基因的表达，提示rIsm 1通过诱导Tbkl 1-Irf 3-Ifn途径促进I型IFN基因和Mxa基因的表达。这些数据共同表明，Isml是一种新的免疫相关因子，在抗病毒免疫应答中起作用，并为控制病毒感染提供了靶点。
Isthmin1 (Ism1), first identified as a secreted protein in Xenopus embryos in 2002, has been shown to perform multiple biological functions, but little is known currently regarding its role in immunity. Here we show that the expression of ism/is inducible by challenge with Grass carp reovirus (GCRV) in zebrafish, suggesting involvement of Ism1 in antiviral response. We then demonstrate that recombinant Ism1 (rIsm1) reduces the cytopathic effect in the cells infected by GCRV, promotes the expression of type I IFN gene and IFN-inducible antiviral protein Mxa gene, and reduces the virus quantity in virus-infected cells and host. We also show that rIsm1 promotes the expression of tbk1, irf3 and irf7, suggesting it promotes the expression of type I IFN gene and Mxa gene via induction of Tbkl1-Irf3-Ifn pathway. These data together indicate that Isml is a new immune-relevant factor functioning in antiviral immune response, and provides a target for controlling viral infection.