Duck plague virus US3 kinase phosphorylates and induces STING degradation to inhibit innate immune responses
Duck plague virus (DPV) causes the highest mortality rate among aquatic birds; however, its antago nistic mechanism against antiviral innate immune responses remains elusive. In this study, we systematically screened and found that most DPV genes have inhibitory potential for duck cyclic guanosine m...
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Elsevier
2025-08-01
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| Series: | Poultry Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0032579125005796 |
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| author | Bin Tian Yanming Tian Dongjie Cai Huanhuan Cao Liping Wu Mingshu Wang Qiao Yang Ying Wu Renyong Jia Dekang Zhu Mafeng Liu Shun Chen Xinxin Zhao Shaqiu Zhang Juan Huang Di Sun Xumin Ou Zhen Wu Anchun Cheng |
| author_facet | Bin Tian Yanming Tian Dongjie Cai Huanhuan Cao Liping Wu Mingshu Wang Qiao Yang Ying Wu Renyong Jia Dekang Zhu Mafeng Liu Shun Chen Xinxin Zhao Shaqiu Zhang Juan Huang Di Sun Xumin Ou Zhen Wu Anchun Cheng |
| author_sort | Bin Tian |
| collection | DOAJ |
| description | Duck plague virus (DPV) causes the highest mortality rate among aquatic birds; however, its antago nistic mechanism against antiviral innate immune responses remains elusive. In this study, we systematically screened and found that most DPV genes have inhibitory potential for duck cyclic guanosine monophosphate-adenosine monophosphate synthetase (cGAS)/stimulator of interferon (IFN) gene (STING) pathway-mediated antiviral responses, with the DPV US3 kinase showing the strongest inhibitory activity. Co-immunoprecipitation and immunoblotting assays demonstrated that DPV US3 interacted with STING and induced its degradation. Further mutagenesis experiments revealed that DPV US3 kinase activity was essential for phosphorylating STING, reducing STING dimerization, and inhibiting STING-mediated antiviral responses. Sequence alignment and mutagenesis studies have demonstrated that DPV US3 phosphorylates STING at serine 86, near the Endoplasmic reticulum (ER) retention sequence (R82YRGS86), disrupting its association with tank-binding kinase 1 (TBK1) and inducing STING degradation. Finally, US3 knockout attenuated DPV replication by activating higher levels of IFN and ISGs in vitro and in vivo. These results demonstrate that DPV promotes viral infection and pathogenicity by inducing STING degradation through the encoded US3 kinase, providing new insights into the mechanism of DPV immune evasion. |
| format | Article |
| id | doaj-art-58f84f883fc54ddfa18dc6630a76b067 |
| institution | Kabale University |
| issn | 0032-5791 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Poultry Science |
| spelling | doaj-art-58f84f883fc54ddfa18dc6630a76b0672025-08-20T03:51:30ZengElsevierPoultry Science0032-57912025-08-01104810533610.1016/j.psj.2025.105336Duck plague virus US3 kinase phosphorylates and induces STING degradation to inhibit innate immune responsesBin Tian0Yanming Tian1Dongjie Cai2Huanhuan Cao3Liping Wu4Mingshu Wang5Qiao Yang6Ying Wu7Renyong Jia8Dekang Zhu9Mafeng Liu10Shun Chen11Xinxin Zhao12Shaqiu Zhang13Juan Huang14Di Sun15Xumin Ou16Zhen Wu17Anchun Cheng18Engineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, ChinaEngineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China; Veterinary Department in College of Aminal Science, State Key Laboratory of Green Pesticide, Institute of Veterinary Immunology and Green Drugs, Guizhou University, Guiyang 550025, China; Corresponding author at: Engineering Research Center of Southwest Animal Disease Prevention and Control Technology for Ministry of Education of the People's Republic of China, International Joint Research Center for Animal Disease Prevention and Control of Sichuan Province, Key Laboratory of Animal Disease and Human Health of Sichuan Province, Research Center of Avian Disease and Institute of Veterinary Medicine and Immunology, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China.Duck plague virus (DPV) causes the highest mortality rate among aquatic birds; however, its antago nistic mechanism against antiviral innate immune responses remains elusive. In this study, we systematically screened and found that most DPV genes have inhibitory potential for duck cyclic guanosine monophosphate-adenosine monophosphate synthetase (cGAS)/stimulator of interferon (IFN) gene (STING) pathway-mediated antiviral responses, with the DPV US3 kinase showing the strongest inhibitory activity. Co-immunoprecipitation and immunoblotting assays demonstrated that DPV US3 interacted with STING and induced its degradation. Further mutagenesis experiments revealed that DPV US3 kinase activity was essential for phosphorylating STING, reducing STING dimerization, and inhibiting STING-mediated antiviral responses. Sequence alignment and mutagenesis studies have demonstrated that DPV US3 phosphorylates STING at serine 86, near the Endoplasmic reticulum (ER) retention sequence (R82YRGS86), disrupting its association with tank-binding kinase 1 (TBK1) and inducing STING degradation. Finally, US3 knockout attenuated DPV replication by activating higher levels of IFN and ISGs in vitro and in vivo. These results demonstrate that DPV promotes viral infection and pathogenicity by inducing STING degradation through the encoded US3 kinase, providing new insights into the mechanism of DPV immune evasion.http://www.sciencedirect.com/science/article/pii/S0032579125005796Alpha herpesvirusUS3 kinaseSTINGPhosphorylationImmune evasion |
| spellingShingle | Bin Tian Yanming Tian Dongjie Cai Huanhuan Cao Liping Wu Mingshu Wang Qiao Yang Ying Wu Renyong Jia Dekang Zhu Mafeng Liu Shun Chen Xinxin Zhao Shaqiu Zhang Juan Huang Di Sun Xumin Ou Zhen Wu Anchun Cheng Duck plague virus US3 kinase phosphorylates and induces STING degradation to inhibit innate immune responses Poultry Science Alpha herpesvirus US3 kinase STING Phosphorylation Immune evasion |
| title | Duck plague virus US3 kinase phosphorylates and induces STING degradation to inhibit innate immune responses |
| title_full | Duck plague virus US3 kinase phosphorylates and induces STING degradation to inhibit innate immune responses |
| title_fullStr | Duck plague virus US3 kinase phosphorylates and induces STING degradation to inhibit innate immune responses |
| title_full_unstemmed | Duck plague virus US3 kinase phosphorylates and induces STING degradation to inhibit innate immune responses |
| title_short | Duck plague virus US3 kinase phosphorylates and induces STING degradation to inhibit innate immune responses |
| title_sort | duck plague virus us3 kinase phosphorylates and induces sting degradation to inhibit innate immune responses |
| topic | Alpha herpesvirus US3 kinase STING Phosphorylation Immune evasion |
| url | http://www.sciencedirect.com/science/article/pii/S0032579125005796 |
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