{"title":"Mandarin fish von Hippel-Lindau protein regulates the NF-κB signaling pathway via interaction with IκB to promote fish ranavirus replication.","authors":"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","doi":"10.24272/j.issn.2095-8137.2023.392","DOIUrl":null,"url":null,"abstract":"<p><p>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 ( <i>Siniperca chuatsi</i>) VHL ( <i>sc</i>VHL) in the NF-κB signaling pathway and mandarin fish ranavirus (MRV) replication were explored. The transcription of <i>sc</i>VHL 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 <i>sc</i>VHL evoked and positively regulated the NF-κB signaling pathway. Treatment with NF-κB signaling pathway inhibitors indicated that the role of <i>sc</i>VHL may be mediated through <i>sc</i>IKKα, <i>sc</i>IKKβ, <i>sc</i>IκBα, or <i>sc</i>p65. Co-immunoprecipitation (Co-IP) analysis identified <i>sc</i>IκBα as a novel target protein of <i>sc</i>VHL. Moreover, <i>sc</i>VHL targeted <i>sc</i>IκBα to 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 <i>sc</i>VHL not only positively regulates NF-κB but also significantly enhances MRV replication. This study reveals a novel function of <i>sc</i>VHL in NF-κB signaling and viral infection in fish.</p>","PeriodicalId":48636,"journal":{"name":"Zoological Research","volume":"45 5","pages":"990-1000"},"PeriodicalIF":4.0000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491782/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Zoological Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.24272/j.issn.2095-8137.2023.392","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ZOOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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 scIκBα as a novel target protein of scVHL. Moreover, scVHL targeted scIκBα to 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.
期刊介绍:
Established in 1980, Zoological Research (ZR) is a bimonthly publication produced by Kunming Institute of Zoology, the Chinese Academy of Sciences, and the China Zoological Society. It publishes peer-reviewed original research article/review/report/note/letter to the editor/editorial in English on Primates and Animal Models, Conservation and Utilization of Animal Resources, and Animal Diversity and Evolution.