Grass carp reovirus VP6 inhibits IFN production by degrading TBK1 through the autophagy pathway

IF 4.1 2区农林科学 Q1 FISHERIES

Fish & shellfish immunology Pub Date : 2025-07-10 DOI:10.1016/j.fsi.2025.110559

Xiao Xu , Zhuo-Cong Li , Bao-Jie Cui , Can Zhang , Na Xu , Yang-Yang Wang , Dan-Dan Chen , Long-Feng Lu , Shun Li

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引用次数: 0

Abstract

The interferon (IFN) response serves as a powerful defense mechanism against viral infections in fish. However, grass carp reovirus (GCRV) is capable of evading the IFN system, although the specific mechanisms remain unclear. In this study, we report that GCRV VP6 employs an immune evasion strategy by degrading TANK-binding kinase 1 (TBK1) through the autophagy pathway, thereby inhibiting IFN activation. Firstly, overexpression of VP6 facilitated the replication of GCRV, while, it impeded the activation of the IFN promoter induced by polyinosinic-polycytidylic acid (poly I:C) and GCRV. In addition, VP6 was found to interact with TBK1 and suppress its expression. Treatment with autophagy pathway inhibitors was able to restore TBK1 degradation, indicating that VP6 degrades TBK1 through the autophagy pathway. Furthermore, VP6 significantly attenuated the cellular antiviral response mediated by TBK1, thereby suppressing IFN production. These results demonstrate how GCRV evades the host immune response by exploiting the host autophagy system and provide insight into the underlying molecular mechanisms involved.

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草鱼呼肠孤病毒VP6通过自噬途径降解TBK1抑制IFN的产生

干扰素（IFN）反应是鱼类对抗病毒感染的强大防御机制。然而，草鱼呼肠孤病毒（GCRV）能够逃避IFN系统，尽管具体机制尚不清楚。在本研究中，我们报道了GCRV VP6通过自噬途径降解TANK-binding kinase 1 (TBK1)，从而抑制IFN的激活，从而采用免疫逃避策略。首先，VP6的过表达促进了GCRV的复制，同时阻碍了多肌苷-多胞酸（poly I:C）和GCRV诱导的IFN启动子的激活。此外，VP6被发现与TBK1相互作用并抑制其表达。使用自噬途径抑制剂治疗能够恢复TBK1的降解，这表明VP6通过自噬途径降解TBK1。此外，VP6显著减弱TBK1介导的细胞抗病毒反应，从而抑制IFN的产生。这些结果证明了GCRV如何利用宿主自噬系统逃避宿主免疫反应，并提供了有关潜在分子机制的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Fish & shellfish immunology 农林科学-海洋与淡水生物学

CiteScore

7.50

自引率

19.10%

发文量

750

审稿时长

68 days

期刊介绍： Fish and Shellfish Immunology rapidly publishes high-quality, peer-refereed contributions in the expanding fields of fish and shellfish immunology. It presents studies on the basic mechanisms of both the specific and non-specific defense systems, the cells, tissues, and humoral factors involved, their dependence on environmental and intrinsic factors, response to pathogens, response to vaccination, and applied studies on the development of specific vaccines for use in the aquaculture industry.