鲤疱疹病毒Ⅱ型ORF4与宿主TLR22b互作调控病毒感染的机制研究

Cyprinid herpesvirus 2 (CyHV-2) causes serious threat to crucian carp and goldfish. The ORF4 protein contains two TNFR domains, which is viral TNFR analog involved in the regulation of inflammatory responses, cell apoptosis and proliferation. Previous studies of this project found that ORF4 regulated virus replication, mediates virus-induced apoptosis, and interacted with CaTLR22b protein. Based on the previous work, this study aims to explore the interaction mechanism between ORF4 and CaTLR22b and its influence on virus infection. Firstly, we try to investigate the regulation of CaTLR22b on CyHV-2 infection by flow cytometry and gene silencing. Then, we try to illustrate the key structural domains of ORF4 and CaTLR22b interaction and studies the regulation rules of their interaction against cyhv-2 infection. Finally, we try to elucidate the mechanism of cyhv-2 infection by studying the regulation of ORF4 and CaTLR22b interaction on the downstream pathway of CaTLR22b. This work will illustrate the mechanism of OFR4 and CaTLR22b in the process of cyhv-2 infection and provide theoretical basis for revealing the mechanism of interaction between virus and its host.

鲤疱疹病毒II型（CyHV-2）是一种对鲫和金鱼造成严重危害的病原。CyHV-2编码的ORF4蛋白含有两个TNFR结构域，是病毒TNFR类似物，该类蛋白参与调控炎症反应、细胞凋亡和增殖。本项目前期研究发现，ORF4调控病毒复制，介导病毒诱导的细胞凋亡，与CaTLR22b蛋白相互作用。本研究拟在前期工作基础上，探索ORF4与CaTLR22b互作机制及其对病毒感染的影响。拟通过流式细胞术和基因沉默等技术研究CaTLR22b对CyHV-2感染的调控；通过解析ORF4与CaTLR22b互作关键结构域，研究二者互作对CyHV-2感染的调控规律；通过研究二者互作对CaTLR22b下游通路的调控，阐明二者互作介导CyHV-2感染的分子机制。该项目实施，有助于揭示OFR4与CaTLR22b在CyHV-2感染过程中的作用机制，为研究病毒与宿主的互作机制提供科学依据。

鲤疱疹病毒II型（CyHV-2）是一种对鲫鱼和金鱼造成严重危害的病原，造成了巨大经济损失，危害鲫鱼养殖业健康发展。然而，CyHV-2侵入宿主细胞的机制研究较少。本项目在前期工作基础上，通过研究ORF4与TLR22b互作机制及其对病毒感染的影响，解析了CyHV-2与宿主互作机制。取得的研究成果如下：（1）鲫鱼的TLR22b促进CyHV-2复制；（2）宿主TLR22b与CyHV-2编码的ORF4互作；（3）ORF4的2个TNFR结构域均不影响ORF4与TLR22b的互作，TLR22b的TIR是TLR22b与ORF4互作的关键结构域；（4）ORF4通过与TLR22b互作调控TLR22b/NF-κB信号通路。本项目对深入研究CyHV-2感染致病机理，阐明病毒与宿主互作过程，鱼类病毒病防控技术具有重要的理论意义。