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 ism1 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 Tbk1–Irf3–Ifn pathway. These data together indicate that Ism1 is a new immune-relevant factor functioning in antiviral immune response, and provides a target for controlling viral infection.

Isthmin1 (Ism1) 于 2002 年首次被鉴定为非洲爪蟾胚胎中的一种分泌蛋白，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，我们显示 ism1 的表达可通过斑马鱼中草鱼呼肠孤病毒 (GCRV) 的攻击诱导，表明 Ism1 参与抗病毒反应。然后，我们证明重组 Ism1 (rIsm1) 可降低 GCRV 感染细胞的细胞病变效应，促进 I 型 IFN 基因和 IFN 诱导型抗病毒蛋白 Mxa 基因的表达，并减少病毒感染细胞和宿主中的病毒数量。我们还表明 rIsm1 促进了tbk1、irf3和 i rf7的表达，表明它通过诱导 Tbk1-Irf3-Ifn 通路促进 I 型 IFN 基因和 Mxa 基因的表达。这些数据共同表明Ism1是一种新的免疫相关因子，在抗病毒免疫反应中发挥作用，并为控制病毒感染提供了靶点。