AUTHOR=Sun Jiya , Wang Jingfeng , Yuan Xuye , Wu Xiangwei , Sui Tianqi , Wu Aiping , Cheng Genhong , Jiang Taijiao 

TITLE=Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02007

DOI=10.3389/fmicb.2019.02007

ISSN=1664-302X

ABSTRACT=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.