Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication  

作　　者：Zhi-Min Li Xiao-Wei Qin Qi Zhang Jian He Min-Cong Liang Chuan-Rui Li Yang Yu Weng-Hui Liu Shao-Ping Weng Jian-Guo He Chang-Jun Guo 

机构地区：[1]School of Marine Sciences,State Key Laboratory for Biocontrol,Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai),Guangdong Province Key Laboratory of Aquatic Economic Animals&Guangdong Provincial Observation and Research Station for Marine Ranching of the Lingdingyang Bay,Sun Yat-sen University,Guangzhou,Guangdong 510275,China [2]Guangdong Laboratory for Lingnan Modern Agriculture,South China Agricultural University,Guangzhou,Guangdong 510640,China

出　　处：《Zoological Research》2024年第5期990-1000,共11页动物学研究（英文）

基　　金：supported by the National Key Research and Development Program of China(2022YFE0203900);Guangdong Key Research and Development Program(2021B0202040002 and 2022B1111030001);China Agriculture Research System(CARS-46);Guangdong Basic and Applied Basic Research Foundation(2021A1515010647);Basic and Applied Basic Research Project of Guangzhou Science and Technology Plan Project(202102020299);Science and Technology Planning Project of Guangdong(2023B1212060023);Guangdong Laboratory for Lingnan Modern Agriculture(NZ2021018)。

摘　　要：The von Hippel-Lindau tumor suppressor protein(VHL),an E3 ubiquitin ligase,functions as a critical regulator of the oxygen-sensing pathway for targeting hypoxia-inducible factors.Recent evidence suggests that mammalian VHL may also be critical to the NF-κB signaling pathway,although the specific molecular mechanisms remain unclear.Herein,the roles of mandarin fish(Siniperca chuatsi)VHL(scVHL)in the NF-κB signaling pathway and mandarin fish ranavirus(MRV)replication were explored.The transcription of scVHL was induced by immune stimulation and MRV infection,indicating a potential role in innate immunity.Dual-luciferase reporter gene assays and reverse transcription quantitative PCR(RT-qPCR)results demonstrated that scVHL evoked and positively regulated the NF-κB signaling pathway.Treatment with NF-κB signaling pathway inhibitors indicated that the role of scVHL may be mediated through scIKKα,scIKKβ,scIκBα,or scp65.Co-immunoprecipitation(Co-IP)analysis identified scIκBαas a novel target protein of scVHL.Moreover,scVHL targeted scIκBαto catalyze the formation of K63-linked polyubiquitin chains to activate the NF-κB signaling pathway.Following MRV infection,NF-κB signaling remained activated,which,in turn,promoted MRV replication.These findings suggest that scVHL not only positively regulates NF-κB but also significantly enhances MRV replication.This study reveals a novel function of scVHL in NF-κB signaling and viral infection in fish.

关 键 词：VHL NF-κB IΚBΑ RANAVIRUS Mandarin fish 

分 类 号：S943[农业科学—水产养殖]