Functional and expression analysis reveals the involvement of integrin αvβ3 in antiviral immunity of grass carp (Ctenopharyngodon idella).
Functional and expression analysis reveals the involvement of integrin αvβ3 in antiviral immunity of grass carp (Ctenopharyngodon idella).
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DOI：
10.1016/j.fsi.2022.08.036
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发表时间：
2022-08
影响因子：
4.7
通讯作者：
Xiao-yan Xiong;Hong-Ge Yang;Chunhua Ding;Beibei Qin;Yadong Deng;L. Xiong;Xiaoyang Liu;Yaoguo Li-Ya
中科院分区：
文献类型：
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作者：
Xiao-yan Xiong;Hong-Ge Yang;Chunhua Ding;Beibei Qin;Yadong Deng;L. Xiong;Xiaoyang Liu;Yaoguo Li-Ya
整合素是一种α-β异源二聚体细胞受体，可与病原体蛋白质结合，在哺乳动物免疫应答中发挥重要作用，但在硬骨鱼中整合素介导的免疫功能尚不清楚。本研究从草鱼Ctenopharyngodonidella中鉴定出一种整合素αvβ3（GCαvβ3），它最初由αv（GCαv）和β3（GCβ3）亚基组装而成。成对比对分析表明，GCαv和GCβ3的氨基酸序列与其他脊椎动物的同源物具有较高的相似性（75.2-95.1%）和同一性（58.6-90.7%）。GCαv和GCβ3均具有保守的蛋白结构域和基序，在包含各种脊椎动物对应物的系统发育树中聚在鱼类分支中。免疫共沉淀显示GCβ3与草鱼呼肠孤病毒（GCRV）外壳蛋白VP 5有相互作用。两个孵育实验表明，GCRV或VP 5蛋白与GCβ3的相互作用可诱导草鱼卵巢细胞系中I型干扰素（IFN）2和IFN 3的表达。功能分析表明，GCαvβ3与人整合素αvβ3一样，是病毒蛋白组分的受体，参与抗病毒免疫。此外，感染GCRV后，草鱼各组织中GCαv和GCβ3均显著上调。本研究为深入了解GCαvβ3的分子特征和免疫功能提供了基础，并为深入研究草鱼整合素特异性抗病毒免疫机制提供了新的思路。
Integrins are α-β heterodimeric cell receptors that can bind the protein components of pathogens, and play crucial roles in mammalian immune responses, but the immune functions mediated by integrins remains largely unknown in teleost fish. In this study, an integrin αvβ3 (GCαvβ3) originally assembled by αv (GCαv) and β3 (GCβ3) subunits, was identified from a teleost fish grass carpCtenopharyngodon idella. The pairwise alignment analyses showed that the amino acid sequences of GCαv and GCβ3 shared high similarity (75.2–95.1%) and identity (58.6–90.7%) with their homologs from other vertebrates. Both GCαv and GCβ3 harbored the conserved protein domains and motifs, and were clustered in fish branch of the phylogenetic tree containing the counterparts from various vertebrates. Co-immunoprecipitation displayed that GCβ3 could interact with the grass carp reovirus (GCRV) outer capsid protein VP5. Two incubation experiments revealed that the interaction of GCRV or VP5 proteins with GCβ3 could induce the expressions of type I interferons (IFNs) including IFN2 and IFN3 in grass carp ovary cell line. The functional analysis demonstrated that GCαvβ3 served as a receptor of viral protein components to be involved in antiviral immunity as human integrin αvβ3 did. In addition, both GCαv and GCβ3 were significantly upregulated in various tissues of grass carp after GCRV infection. This study might provide fundamental basis for understanding the molecular characteristics and immune functions of GCαvβ3, and offer a new insight into the antiviral immune mechanism specific to the integrins in grass carp.