College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China; Freshwater Aquaculture Collaborative Innovation Center of Hubei Province, Wuhan, 430070, China; Hubei Engineering Technology Research Center for Aquatic Animal Diseases Control and Prevention, Wuhan, 430070, China.
Department of Public Health Sciences, University of Hawaii at Manoa, Honolulu, HI, USA.
Fish Shellfish Immunol. 2019 Mar;86:805-813. doi: 10.1016/j.fsi.2018.12.012. Epub 2018 Dec 9.
Viperin is known to play an important role in innate immune and its antiviral mechanisms are well demonstrated in mammals. Fish Viperin mediates antiviral activity against several viruses. However, little has been done to the underlying mechanism. Here, we discovered a novel Viperin splice variant named Viperin_sv1 from viral-infected FHM cells. Spring varimia of carp virus (SVCV) was able to increase the mRNA levels of both Viperin and Viperin_sv1, while poly(I:C) only has effect on Viperin. Viperin functions as an antiviral protein at 24 h post-SVCV infection, but the antiviral activity dramatically declined at late infection stages. However, Viperin_sv1 inhibited SVCV replication significantly at all the tested time. Viperin_sv1, but not Viperin can facilitate the production of type I IFN and IFN stimulate genes (ISGs) through activation of RIG-1, IRF3 and IRF7 signaling cascades. On the other hand, SVCV down-regulated Viperin_sv1 at the protein level through the proteasome pathway to keep itself away from the immune system monitoring. Taken together, these findings provide new insights into the regulation of Viperin from the posttranscriptional modification perspective and the role of splicing variant Viperin_sv1 in virus-host interaction.
Viperin 在先天免疫中发挥着重要作用，其抗病毒机制在哺乳动物中得到了很好的证明。鱼类 Viperin 介导了针对多种病毒的抗病毒活性。然而，对于其潜在的机制还知之甚少。在这里，我们从病毒感染的 FHM 细胞中发现了一种名为 Viperin_sv1 的新型 Viperin 剪接变体。鲤鱼 Spring 贫血症病毒 (SVCV) 能够增加 Viperin 和 Viperin_sv1 的 mRNA 水平，而 poly(I:C) 仅对 Viperin 有作用。Viperin 在 SVCV 感染后 24 小时发挥抗病毒蛋白的作用，但在晚期感染阶段，其抗病毒活性显著下降。然而，Viperin_sv1 在所有测试时间都显著抑制了 SVCV 的复制。Viperin_sv1 而不是 Viperin 可以通过激活 RIG-1、IRF3 和 IRF7 信号级联来促进 I 型 IFN 和 IFN 刺激基因 (ISGs) 的产生。另一方面，SVCV 通过蛋白酶体途径下调 Viperin_sv1 的蛋白水平，使其免受免疫系统的监测。总之，这些发现从转录后修饰的角度提供了对 Viperin 调节的新见解，以及剪接变体 Viperin_sv1 在病毒-宿主相互作用中的作用。
