Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus
Avian influenza A viruses (IAV) can cross the species barrier and cause disease in humans. Understanding the pathogenesis of avian IAV remains a challenge. Interferon-mediated antiviral responses and multiple cytokines production are important host cellular antiviral immunity against IAV infection....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-09-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.02007/full |
| _version_ | 1811262137737150464 |
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| author | Jiya Sun Jiya Sun Jingfeng Wang Jingfeng Wang Xuye Yuan Xuye Yuan Xiangwei Wu Xiangwei Wu Tianqi Sui Tianqi Sui Aiping Wu Aiping Wu Genhong Cheng Genhong Cheng Genhong Cheng Taijiao Jiang Taijiao Jiang |
| author_facet | Jiya Sun Jiya Sun Jingfeng Wang Jingfeng Wang Xuye Yuan Xuye Yuan Xiangwei Wu Xiangwei Wu Tianqi Sui Tianqi Sui Aiping Wu Aiping Wu Genhong Cheng Genhong Cheng Genhong Cheng Taijiao Jiang Taijiao Jiang |
| author_sort | Jiya Sun |
| collection | DOAJ |
| description | Avian influenza A viruses (IAV) can cross the species barrier and cause disease in humans. Understanding the pathogenesis of avian IAV remains a challenge. Interferon-mediated antiviral responses and multiple cytokines production are important host cellular antiviral immunity against IAV infection. To elucidate the pathogenicity of avian IAV, a system approach was adopted to investigate dysregulation of the two host cellular antiviral immune responses in contrast with human IAV. As a result, we revealed that avian IAV not only disrupted normal early host cellular interferon-mediated antiviral responses, but also caused abnormal cytokines production through different pathways. For avian IAV infection, dysregulation of STAT2 was mainly responsible for abnormal cellular interferon-mediated antiviral responses, and IRF5 and NFKB1 played crucial roles in unusual cytokines production. In contrast, for human IAV infection, IRF1, IRF7, and STAT1 contributed to cellular cytokines production. Furthermore, differential activation of pattern recognition receptors (PRRs) likely led to avian IAV-related abnormal early host cellular antiviral immunity, where TLR7 and RIG-I were activated by avian and human IAV, respectively. Finally, a pathogenesis model was proposed that combined of early host cellular interferon-mediated antiviral responses with cytokines production could partly explain the pathogenicity of avian IAV. In conclusion, our study provides a new perspective of the pathogenesis of avian IAV, which will be helpful in preventing their infections in the future. |
| first_indexed | 2024-04-12T19:18:38Z |
| format | Article |
| id | doaj.art-cee1c4e2ee8e43cba894faa3ab0e0dc4 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T19:18:38Z |
| publishDate | 2019-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-cee1c4e2ee8e43cba894faa3ab0e0dc42022-12-22T03:19:39ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-09-011010.3389/fmicb.2019.02007470224Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A VirusJiya Sun0Jiya Sun1Jingfeng Wang2Jingfeng Wang3Xuye Yuan4Xuye Yuan5Xiangwei Wu6Xiangwei Wu7Tianqi Sui8Tianqi Sui9Aiping Wu10Aiping Wu11Genhong Cheng12Genhong Cheng13Genhong Cheng14Taijiao Jiang15Taijiao Jiang16Suzhou Institute of Systems Medicine, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaSuzhou Institute of Systems Medicine, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaSuzhou Institute of Systems Medicine, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaSuzhou Institute of Systems Medicine, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaSuzhou Institute of Systems Medicine, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaSuzhou Institute of Systems Medicine, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaSuzhou Institute of Systems Medicine, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United StatesSuzhou Institute of Systems Medicine, Suzhou, ChinaCenter for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, ChinaAvian influenza A viruses (IAV) can cross the species barrier and cause disease in humans. Understanding the pathogenesis of avian IAV remains a challenge. Interferon-mediated antiviral responses and multiple cytokines production are important host cellular antiviral immunity against IAV infection. To elucidate the pathogenicity of avian IAV, a system approach was adopted to investigate dysregulation of the two host cellular antiviral immune responses in contrast with human IAV. As a result, we revealed that avian IAV not only disrupted normal early host cellular interferon-mediated antiviral responses, but also caused abnormal cytokines production through different pathways. For avian IAV infection, dysregulation of STAT2 was mainly responsible for abnormal cellular interferon-mediated antiviral responses, and IRF5 and NFKB1 played crucial roles in unusual cytokines production. In contrast, for human IAV infection, IRF1, IRF7, and STAT1 contributed to cellular cytokines production. Furthermore, differential activation of pattern recognition receptors (PRRs) likely led to avian IAV-related abnormal early host cellular antiviral immunity, where TLR7 and RIG-I were activated by avian and human IAV, respectively. Finally, a pathogenesis model was proposed that combined of early host cellular interferon-mediated antiviral responses with cytokines production could partly explain the pathogenicity of avian IAV. In conclusion, our study provides a new perspective of the pathogenesis of avian IAV, which will be helpful in preventing their infections in the future.https://www.frontiersin.org/article/10.3389/fmicb.2019.02007/fullinfluenzavirus–host interactionearly immune responsegene networkinterferon |
| spellingShingle | Jiya Sun Jiya Sun Jingfeng Wang Jingfeng Wang Xuye Yuan Xuye Yuan Xiangwei Wu Xiangwei Wu Tianqi Sui Tianqi Sui Aiping Wu Aiping Wu Genhong Cheng Genhong Cheng Genhong Cheng Taijiao Jiang Taijiao Jiang Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus Frontiers in Microbiology influenza virus–host interaction early immune response gene network interferon |
| title | Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus |
| title_full | Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus |
| title_fullStr | Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus |
| title_full_unstemmed | Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus |
| title_short | Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus |
| title_sort | regulation of early host immune responses shapes the pathogenicity of avian influenza a virus |
| topic | influenza virus–host interaction early immune response gene network interferon |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.02007/full |
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