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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Microbiol. | doi: 10.3389/fmicb.2019.02007

Regulation of early host immune responses shapes the pathogenicity of avian influenza A virus

 Jiya Sun1*,  Jingfeng Wang1, Xuye Yuan1,  Xiangwei Wu1, Tianqi Sui1,  Aiping Wu1,  Genhong Cheng1 and Taijiao Jiang1
  • 1Center of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou Institute of Systems Medicine (ISM), China

Understanding the pathogenesis of avian influenza A virus remains a challenge. Influenza A virus (IAV) can elicit two major types of early host immune responses including interferon-mediated antiviral genes and multiple cytokines. To elucidate the pathogenicity of avian IAV, we took a system approach to investigate dysregulation of the two early host immune responses in contrast to human IAV. As a result, we revealed that avian IAV not only disrupted normal early host interferon-mediated antiviral responses, but also took different pathways to induce cytokines. For avian IAV infection, dysregulation of STAT2 was mainly responsible for abnormal antiviral responses, and IRF5 and NFKB1 played crucial roles in unusual cytokine production. In contrast, IRF1, IRF7 and STAT1 contributed to human IAV induced cytokine production. Furthermore, differential activation of pattern recognition receptor likely caused avian IAV induced abnormal early host immune responses, where TLR7 and RIG-I were activated by avian and human IAV, respectively. Finally, we proposed a pathogenesis model that combined early host interferon-mediated antiviral responses and cytokine production for explaining the pathogenicity of avian IAV. In conclusion, our study provided a new perspective of the pathogenesis of avian IAV, which will be helpful for their prevention in the future.

Keywords: virus host interaction, early immune response, Gene network, avian influenza, interferon

Received: 14 Jun 2019; Accepted: 15 Aug 2019.

Copyright: © 2019 Sun, Wang, Yuan, Wu, Sui, Wu, Cheng and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Jiya Sun, Center of Systems Medicine, Chinese Academy of Medical Sciences, Suzhou Institute of Systems Medicine (ISM), Suzhou, China, biosyssun@163.com