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题名: Zebrafish foxo3b Negatively Regulates Antiviral Response through Suppressing the Transactivity of irf3 and irf7
作者: Liu, Xing1; Cai, Xiaolian1; Zhang, Dawei1; Xu, Chenxi1; Xiao, Wuhan1, 2
刊名: JOURNAL OF IMMUNOLOGY
发表日期: 2016-12-15
DOI: 10.4049/jimmunol.1601187
卷: 197, 期:12, 页:4736-4749
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
类目[WOS]: Immunology
研究领域[WOS]: Immunology
英文摘要: Forkhead box O (FOXO)3, a member of the FOXO family of transcription factors, plays key roles in various cellular processes, including development, longevity, reproduction, and metabolism. Recently, FOXO3 has also been shown to be involved in modulating the immune response. However, how FOXO3 regulates immunity and the underlying mechanisms are still largely unknown. In this study, we show that zebrafish (Danio rerio) foxo3b, an ortholog of mammalian FOXO3, is induced by polyinosinic-polycytidylic acid stimulation and spring viremia of carp virus (SVCV) infection. We found that foxo3b interacted with irf3 and irf7 to inhibit ifr3/irf7 transcriptional activity, thus resulting in suppression of SVCV or polyinosinic-polycytidylic acid-induced IFN activation. By suppressing expression of key antiviral genes, foxo3b negatively regulated the cellular antiviral response. Furthermore, upon SVCV infection, the expression of the key antiviral genes was significantly enhanced in foxo3b-null zebrafish larvae compared with wild-type larvae. Additionally, the replication of SVCV was inhibited in foxo3b-null zebrafish larvae, leading to a higher survival rate. Our findings suggest that by suppressing irf3/irf7 activity, zebrafish foxo3b negatively regulates the antiviral response, implicating the vital role of the FOXO gene family in innate immunity.
关键词[WOS]: FORKHEAD TRANSCRIPTION FACTOR ; DEPENDENT PROTEIN-KINASE ; OXIDATIVE STRESS ; INNATE IMMUNITY ; TELEOST FISH ; KAPPA-B ; INTERFERON ; METHYLATION ; ACTIVATION ; RECEPTORS
语种: 英语
项目资助者: Chinese Academy of Sciences Major Scientific and Technological Project(XDA08010208) ; National Natural Science Foundation of China(31461163003 ; 31671315 ; 91631102 ; 31401072)
WOS记录号: WOS:000389635900024
ISSN号: 0022-1767
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/28748
Appears in Collections:水生生物分子与细胞生物学研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, Key Lab Aquat Biodivers & Conservat, Wuhan 430072, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China
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