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

[tetano]

Front Microbiol. 2019 Sep 11;10:2007. doi: 10.3389/fmicb.2019.02007. eCollection 2019. Regulation of Early Host Immune Responses Shapes the Pathogenicity of Avian Influenza A Virus.

Sun J^1,2, Wang J^1,2, Yuan X^1,2, Wu X^1,2, Sui T^1,2, Wu A^1,2, Cheng G^1,2,3, Jiang T^1,2.
Author information

1 Suzhou Institute of Systems Medicine, Suzhou, China. 2 Center for Systems Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. 3 Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

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.
Copyright ? 2019 Sun, Wang, Yuan, Wu, Sui, Wu, Cheng and Jiang.


KEYWORDS:

early immune response; gene network; influenza; interferon; virus–host interaction

PMID: 31572308 PMCID: PMC6749051 DOI: 10.3389/fmicb.2019.02007
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