Neddylation Facilitates the Antiviral Response in Zebrafish
Neddylation is a type of post-translational protein modifications, in which neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) is covalently conjugated to the lysine residues of target substrates. The best characterized principal substrates of neddylation are the cullin-...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01432/full |
| _version_ | 1817985108159758336 |
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| author | Guangqing Yu Guangqing Yu Guangqing Yu Guangqing Yu Xing Liu Xing Liu Xing Liu Jinhua Tang Jinhua Tang Jinhua Tang Jinhua Tang Chenxi Xu Chenxi Xu Chenxi Xu Gang Ouyang Gang Ouyang Gang Ouyang Wuhan Xiao Wuhan Xiao Wuhan Xiao Wuhan Xiao Wuhan Xiao |
| author_facet | Guangqing Yu Guangqing Yu Guangqing Yu Guangqing Yu Xing Liu Xing Liu Xing Liu Jinhua Tang Jinhua Tang Jinhua Tang Jinhua Tang Chenxi Xu Chenxi Xu Chenxi Xu Gang Ouyang Gang Ouyang Gang Ouyang Wuhan Xiao Wuhan Xiao Wuhan Xiao Wuhan Xiao Wuhan Xiao |
| author_sort | Guangqing Yu |
| collection | DOAJ |
| description | Neddylation is a type of post-translational protein modifications, in which neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) is covalently conjugated to the lysine residues of target substrates. The best characterized principal substrates of neddylation are the cullin-RING ligases (CRLs). In addition, neddylation also modifies non-cullin proteins to affect gene regulation, cell survival, organ development, and stress response. However, the role of neddylation in antiviral innate immunity remain largely unknown. Here, we found that when neddylation was blocked by the NEDD8 activating enzyme E1 (NAE) inhibitor, MLN4924, the cellular and organismal antiviral response was suppressed. Moreover, the disruption of nedd8 increased the sensitivity of zebrafish to SVCV infection. Further assays indicated that blocking or silencing neddylation significantly downregulated key antiviral genes after poly (I:C) stimulation or SVCV infection, but dramatically increased SVCV replication. Neddylation of Irf3 and Irf7 was readily detected, but not of Mda5, Mavs, and Tbk1. Thus, our results not only demonstrated that neddylation facilitated the antiviral response in vitro and in vivo, but also revealed a novel role of nedd8 in antiviral innate immunity. |
| first_indexed | 2024-04-13T23:52:58Z |
| format | Article |
| id | doaj.art-c0d5d115758e4519b3c8fe8c65af1a30 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T23:52:58Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-c0d5d115758e4519b3c8fe8c65af1a302022-12-22T02:24:00ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-06-011010.3389/fimmu.2019.01432459970Neddylation Facilitates the Antiviral Response in ZebrafishGuangqing Yu0Guangqing Yu1Guangqing Yu2Guangqing Yu3Xing Liu4Xing Liu5Xing Liu6Jinhua Tang7Jinhua Tang8Jinhua Tang9Jinhua Tang10Chenxi Xu11Chenxi Xu12Chenxi Xu13Gang Ouyang14Gang Ouyang15Gang Ouyang16Wuhan Xiao17Wuhan Xiao18Wuhan Xiao19Wuhan Xiao20Wuhan Xiao21State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaThe Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Wuhan, ChinaThe Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaThe Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Wuhan, ChinaThe Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaThe Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Wuhan, ChinaThe Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaThe Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Wuhan, ChinaThe Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaThe Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Wuhan, ChinaThe Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaState Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaThe Key Laboratory of Aquaculture Disease Control, Ministry of Agriculture, Wuhan, ChinaThe Key Laboratory of Aquatic Biodiversity and Conservation, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, ChinaUniversity of Chinese Academy of Sciences, Beijing, ChinaThe Innovation Academy of Seed Design, Chinese Academy of Sciences, Wuhan, ChinaNeddylation is a type of post-translational protein modifications, in which neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) is covalently conjugated to the lysine residues of target substrates. The best characterized principal substrates of neddylation are the cullin-RING ligases (CRLs). In addition, neddylation also modifies non-cullin proteins to affect gene regulation, cell survival, organ development, and stress response. However, the role of neddylation in antiviral innate immunity remain largely unknown. Here, we found that when neddylation was blocked by the NEDD8 activating enzyme E1 (NAE) inhibitor, MLN4924, the cellular and organismal antiviral response was suppressed. Moreover, the disruption of nedd8 increased the sensitivity of zebrafish to SVCV infection. Further assays indicated that blocking or silencing neddylation significantly downregulated key antiviral genes after poly (I:C) stimulation or SVCV infection, but dramatically increased SVCV replication. Neddylation of Irf3 and Irf7 was readily detected, but not of Mda5, Mavs, and Tbk1. Thus, our results not only demonstrated that neddylation facilitated the antiviral response in vitro and in vivo, but also revealed a novel role of nedd8 in antiviral innate immunity.https://www.frontiersin.org/article/10.3389/fimmu.2019.01432/fullnedd8zebrafishMLN4924antiviral responseinnate immunityneddylation |
| spellingShingle | Guangqing Yu Guangqing Yu Guangqing Yu Guangqing Yu Xing Liu Xing Liu Xing Liu Jinhua Tang Jinhua Tang Jinhua Tang Jinhua Tang Chenxi Xu Chenxi Xu Chenxi Xu Gang Ouyang Gang Ouyang Gang Ouyang Wuhan Xiao Wuhan Xiao Wuhan Xiao Wuhan Xiao Wuhan Xiao Neddylation Facilitates the Antiviral Response in Zebrafish Frontiers in Immunology nedd8 zebrafish MLN4924 antiviral response innate immunity neddylation |
| title | Neddylation Facilitates the Antiviral Response in Zebrafish |
| title_full | Neddylation Facilitates the Antiviral Response in Zebrafish |
| title_fullStr | Neddylation Facilitates the Antiviral Response in Zebrafish |
| title_full_unstemmed | Neddylation Facilitates the Antiviral Response in Zebrafish |
| title_short | Neddylation Facilitates the Antiviral Response in Zebrafish |
| title_sort | neddylation facilitates the antiviral response in zebrafish |
| topic | nedd8 zebrafish MLN4924 antiviral response innate immunity neddylation |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01432/full |
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