The PB1 protein of H9N2 influenza A virus inhibits antiviral innate immunity by targeting MAVS for TRIM25-mediated autophagic degradationThe parent data and images support the findings of this work freely available at

The proteins encoded by Influenza A virus (IAV) evade the innate immune system through diverse strategies to facilitate their replication. However, the regulatory mechanisms remain not fully understood. In this study, we identified that the H9N2 PB1 protein suppressed the activities of the IFN-β, IS...

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Main Authors: Jiawei Luo, Yiyuan Lu, Enqi Dai, Nianchun Yin, Ting Wang, Hongxi Qian, Qingrong Jiang, Xin Cao, Chunfeng Wang, Yan Zeng
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Poultry Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0032579124012173
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author Jiawei Luo
Yiyuan Lu
Enqi Dai
Nianchun Yin
Ting Wang
Hongxi Qian
Qingrong Jiang
Xin Cao
Chunfeng Wang
Yan Zeng
author_facet Jiawei Luo
Yiyuan Lu
Enqi Dai
Nianchun Yin
Ting Wang
Hongxi Qian
Qingrong Jiang
Xin Cao
Chunfeng Wang
Yan Zeng
author_sort Jiawei Luo
collection DOAJ
description The proteins encoded by Influenza A virus (IAV) evade the innate immune system through diverse strategies to facilitate their replication. However, the regulatory mechanisms remain not fully understood. In this study, we identified that the H9N2 PB1 protein suppressed the activities of the IFN-β, ISRE, and NF-κB promoters. Furthermore, H9N2 PB1 inhibited the phosphorylation of IRF3, IκBα, and TBK1 and the secretion of IFN-β. The results demonstrated H9N2 PB1 as a negative regulator of the RIG-I signaling pathway. Subsequent investigations revealed a specific interaction between H9N2 PB1 and MAVS, which disturbed the stability of MAVS. Notably, we discovered that H9N2 PB1 exploited the function of TRIM25, leading to the autophagic degradation of MAVS through K48-linked polyubiquitination. In conclusion, we uncovered a negative regulatory axis consisting of H9N2 PB1-TRIM25-MAVS-IFN-I. These findings provide valuable insights into the molecular interactions involved in the regulation of the host's innate immune antiviral response by IAV.
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issn 0032-5791
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series Poultry Science
spelling doaj-art-bd1f9665257f42a0a214094f349b8a1a2025-01-22T05:40:47ZengElsevierPoultry Science0032-57912025-01-011041104639The PB1 protein of H9N2 influenza A virus inhibits antiviral innate immunity by targeting MAVS for TRIM25-mediated autophagic degradationThe parent data and images support the findings of this work freely available atJiawei Luo0Yiyuan Lu1Enqi Dai2Nianchun Yin3Ting Wang4Hongxi Qian5Qingrong Jiang6Xin Cao7Chunfeng Wang8Yan Zeng9College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, PR ChinaCollege of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, PR China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, 130118, PR China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, PR China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, PR ChinaCollege of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, PR ChinaSuining Municipal Agricultural and Rural Bureau of Sichuan Province, Suining, 629000, PR ChinaCollege of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, PR ChinaTECHLEX Food Co. Ltd, Mianyang, 621000, PR ChinaSichuan Sundaily Farm Ecological Food Co. Ltd, Mianyang, 621000, PR ChinaCollege of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, PR China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, 130118, PR China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, PR China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, PR China; Corresponding authors.College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, PR China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, 130118, PR China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, PR China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, PR China; Corresponding authors.College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, PR China; Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Agricultural University, Changchun, 130118, PR China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, PR China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, PR China; Corresponding authors.The proteins encoded by Influenza A virus (IAV) evade the innate immune system through diverse strategies to facilitate their replication. However, the regulatory mechanisms remain not fully understood. In this study, we identified that the H9N2 PB1 protein suppressed the activities of the IFN-β, ISRE, and NF-κB promoters. Furthermore, H9N2 PB1 inhibited the phosphorylation of IRF3, IκBα, and TBK1 and the secretion of IFN-β. The results demonstrated H9N2 PB1 as a negative regulator of the RIG-I signaling pathway. Subsequent investigations revealed a specific interaction between H9N2 PB1 and MAVS, which disturbed the stability of MAVS. Notably, we discovered that H9N2 PB1 exploited the function of TRIM25, leading to the autophagic degradation of MAVS through K48-linked polyubiquitination. In conclusion, we uncovered a negative regulatory axis consisting of H9N2 PB1-TRIM25-MAVS-IFN-I. These findings provide valuable insights into the molecular interactions involved in the regulation of the host's innate immune antiviral response by IAV.http://www.sciencedirect.com/science/article/pii/S0032579124012173H9N2 PB1MAVSTRIM25Autophagic degradationK48-linked polyubiquitination
spellingShingle Jiawei Luo
Yiyuan Lu
Enqi Dai
Nianchun Yin
Ting Wang
Hongxi Qian
Qingrong Jiang
Xin Cao
Chunfeng Wang
Yan Zeng
The PB1 protein of H9N2 influenza A virus inhibits antiviral innate immunity by targeting MAVS for TRIM25-mediated autophagic degradationThe parent data and images support the findings of this work freely available at
Poultry Science
H9N2 PB1
MAVS
TRIM25
Autophagic degradation
K48-linked polyubiquitination
title The PB1 protein of H9N2 influenza A virus inhibits antiviral innate immunity by targeting MAVS for TRIM25-mediated autophagic degradationThe parent data and images support the findings of this work freely available at
title_full The PB1 protein of H9N2 influenza A virus inhibits antiviral innate immunity by targeting MAVS for TRIM25-mediated autophagic degradationThe parent data and images support the findings of this work freely available at
title_fullStr The PB1 protein of H9N2 influenza A virus inhibits antiviral innate immunity by targeting MAVS for TRIM25-mediated autophagic degradationThe parent data and images support the findings of this work freely available at
title_full_unstemmed The PB1 protein of H9N2 influenza A virus inhibits antiviral innate immunity by targeting MAVS for TRIM25-mediated autophagic degradationThe parent data and images support the findings of this work freely available at
title_short The PB1 protein of H9N2 influenza A virus inhibits antiviral innate immunity by targeting MAVS for TRIM25-mediated autophagic degradationThe parent data and images support the findings of this work freely available at
title_sort pb1 protein of h9n2 influenza a virus inhibits antiviral innate immunity by targeting mavs for trim25 mediated autophagic degradationthe parent data and images support the findings of this work freely available at
topic H9N2 PB1
MAVS
TRIM25
Autophagic degradation
K48-linked polyubiquitination
url http://www.sciencedirect.com/science/article/pii/S0032579124012173
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