Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3
The influenza A virus (IAV) can be recognized by retinoic acid-inducible gene I (RIG-I) to activate the type I interferon response and induce antiviral effects. The virus has evolved several strategies to evade the innate immune response, including non-structural protein 1 (NS1) and its polymerase s...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01051/full |
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| author | Chenyang Yi Chenyang Yi Chenyang Yi Chenyang Yi Zongzheng Zhao Zongzheng Zhao Zongzheng Zhao Zongzheng Zhao Shengyu Wang Shengyu Wang Shengyu Wang Shengyu Wang Xin Sun Xin Sun Xin Sun Xin Sun Dan Zhang Dan Zhang Dan Zhang Dan Zhang Xiaomei Sun Xiaomei Sun Xiaomei Sun Xiaomei Sun Anding Zhang Anding Zhang Anding Zhang Anding Zhang Meilin Jin Meilin Jin Meilin Jin Meilin Jin |
| author_facet | Chenyang Yi Chenyang Yi Chenyang Yi Chenyang Yi Zongzheng Zhao Zongzheng Zhao Zongzheng Zhao Zongzheng Zhao Shengyu Wang Shengyu Wang Shengyu Wang Shengyu Wang Xin Sun Xin Sun Xin Sun Xin Sun Dan Zhang Dan Zhang Dan Zhang Dan Zhang Xiaomei Sun Xiaomei Sun Xiaomei Sun Xiaomei Sun Anding Zhang Anding Zhang Anding Zhang Anding Zhang Meilin Jin Meilin Jin Meilin Jin Meilin Jin |
| author_sort | Chenyang Yi |
| collection | DOAJ |
| description | The influenza A virus (IAV) can be recognized by retinoic acid-inducible gene I (RIG-I) to activate the type I interferon response and induce antiviral effects. The virus has evolved several strategies to evade the innate immune response, including non-structural protein 1 (NS1) and its polymerase subunits. The mechanism by which NS1 inhibits interferon-β (IFN-β) is well understood, whereas the mechanism by which polymerase acid protein (PA) inhibits IFN-β remains to be elucidated. In this study, we observed that the IAV PA protein could inhibit the production of IFN-β and interferon-stimulated genes induced by Sendai virus through interferon regulatory factor 3 (IRF3), but not through nuclear factor-kappaB (NF-kappaB). In addition, PA inhibited IFN-β induction by RIG-I, melanoma differentiation-associated gene 5, mitochondria antiviral signaling protein, TANK-binding kinase 1, inhibitor of nuclear factor kappa-B kinase-ε (IKKε), and IRF3 overexpression. Furthermore, PA interacted with IRF3 to block its activation. The N-terminal endonuclease activity of PA was responsible for its interaction with IRF3 and inhibition of the IFN-β signaling pathway. In summary, our data reveal the mechanism by which IAV PA inhibits the IFN-β signaling pathway, providing a new mechanism by which the virus antagonizes the antiviral signaling pathway. |
| first_indexed | 2024-12-14T03:36:29Z |
| format | Article |
| id | doaj.art-e7d205f03d58490ab97e24b498e4561c |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T03:36:29Z |
| publishDate | 2017-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e7d205f03d58490ab97e24b498e4561c2022-12-21T23:18:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-09-01810.3389/fimmu.2017.01051269279Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3Chenyang Yi0Chenyang Yi1Chenyang Yi2Chenyang Yi3Zongzheng Zhao4Zongzheng Zhao5Zongzheng Zhao6Zongzheng Zhao7Shengyu Wang8Shengyu Wang9Shengyu Wang10Shengyu Wang11Xin Sun12Xin Sun13Xin Sun14Xin Sun15Dan Zhang16Dan Zhang17Dan Zhang18Dan Zhang19Xiaomei Sun20Xiaomei Sun21Xiaomei Sun22Xiaomei Sun23Anding Zhang24Anding Zhang25Anding Zhang26Anding Zhang27Meilin Jin28Meilin Jin29Meilin Jin30Meilin Jin31State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaState Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, ChinaLaboratory of Animal Virology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaKey Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, ChinaThe Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan, ChinaThe influenza A virus (IAV) can be recognized by retinoic acid-inducible gene I (RIG-I) to activate the type I interferon response and induce antiviral effects. The virus has evolved several strategies to evade the innate immune response, including non-structural protein 1 (NS1) and its polymerase subunits. The mechanism by which NS1 inhibits interferon-β (IFN-β) is well understood, whereas the mechanism by which polymerase acid protein (PA) inhibits IFN-β remains to be elucidated. In this study, we observed that the IAV PA protein could inhibit the production of IFN-β and interferon-stimulated genes induced by Sendai virus through interferon regulatory factor 3 (IRF3), but not through nuclear factor-kappaB (NF-kappaB). In addition, PA inhibited IFN-β induction by RIG-I, melanoma differentiation-associated gene 5, mitochondria antiviral signaling protein, TANK-binding kinase 1, inhibitor of nuclear factor kappa-B kinase-ε (IKKε), and IRF3 overexpression. Furthermore, PA interacted with IRF3 to block its activation. The N-terminal endonuclease activity of PA was responsible for its interaction with IRF3 and inhibition of the IFN-β signaling pathway. In summary, our data reveal the mechanism by which IAV PA inhibits the IFN-β signaling pathway, providing a new mechanism by which the virus antagonizes the antiviral signaling pathway.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01051/fullpolymerasepdm/09innate immunitysignaling pathwayphosphorylation |
| spellingShingle | Chenyang Yi Chenyang Yi Chenyang Yi Chenyang Yi Zongzheng Zhao Zongzheng Zhao Zongzheng Zhao Zongzheng Zhao Shengyu Wang Shengyu Wang Shengyu Wang Shengyu Wang Xin Sun Xin Sun Xin Sun Xin Sun Dan Zhang Dan Zhang Dan Zhang Dan Zhang Xiaomei Sun Xiaomei Sun Xiaomei Sun Xiaomei Sun Anding Zhang Anding Zhang Anding Zhang Anding Zhang Meilin Jin Meilin Jin Meilin Jin Meilin Jin Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3 Frontiers in Immunology polymerase pdm/09 innate immunity signaling pathway phosphorylation |
| title | Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3 |
| title_full | Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3 |
| title_fullStr | Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3 |
| title_full_unstemmed | Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3 |
| title_short | Influenza A Virus PA Antagonizes Interferon-β by Interacting with Interferon Regulatory Factor 3 |
| title_sort | influenza a virus pa antagonizes interferon β by interacting with interferon regulatory factor 3 |
| topic | polymerase pdm/09 innate immunity signaling pathway phosphorylation |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01051/full |
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