Cyprinid herpesvirus 2 (CyHV-2) ORF67 inhibits IFN expression by competitively obstructing STING phosphorylation

IF 4.1 2区农林科学 Q1 FISHERIES

Fish & shellfish immunology Pub Date : 2025-04-28 DOI:10.1016/j.fsi.2025.110372

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

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引用次数: 0

Abstract

Cyprinid herpesvirus 2 (CyHV-2) caused hematopoietic necrosis in crucian carp (Carassius auratus) has resulted in huge economic losses to the carp aquaculture. Interferon (IFN) response serves as a crucial line of defense for fish against CyHV-2 infection; however, CyHV-2 frequently overcomes this defense, resulting in damage and even substantial mortality. The mechanism by which CyHV-2 evades the fish IFN antiviral response remains unclear. In this study, we chose the open reading frame 67 (ORF67) of CyHV-2 as the target of our research. Firstly, the results of Co-immunoprecipitation (Co-IP) assay and in vitro phosphorylation showed that the ORF67 inhibited the expression of IFN by binding to TBK1-A/B and competitively blocking STING-A/B phosphorylation. Then, we elaborated on the effect of ORF67 on the cell's antiviral function by cytopathic effect (CPE) and immunoblot analysis. In summary, this study has clarified the molecular mechanism of immune evasion by ORF67 through the inhibition of host IFN expression. This research enhances our understanding of the pathogenesis of CyHV-2 and provides theoretical references for the prevention and treatment of hematopoietic necrosis.

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CyHV-2 ORF67通过竞争性阻断STING磷酸化抑制IFN表达

鲤疱疹病毒2型（CyHV-2）引起的鲫鱼造血坏死给鲫鱼养殖业造成了巨大的经济损失。干扰素（IFN）反应是鱼类抵御CyHV-2感染的关键防线；然而，CyHV-2经常克服这种防御，导致损害甚至大量死亡。CyHV-2逃避鱼类IFN抗病毒反应的机制尚不清楚。在本研究中，我们选择CyHV-2的开放阅读框67 （ORF67）作为我们的研究对象。首先，共免疫沉淀（Co-IP）实验和体外磷酸化实验结果表明，ORF67通过与TBK1-A/B结合，竞争性阻断STING-A/B磷酸化，抑制IFN的表达。然后，我们通过细胞病变效应（CPE）和免疫印迹分析阐述了ORF67对细胞抗病毒功能的影响。综上所述，本研究阐明了ORF67通过抑制宿主IFN表达而逃避免疫的分子机制。本研究增强了我们对CyHV-2发病机制的认识，为预防和治疗造血坏死提供理论参考。

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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.