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The influenza virus PB2 protein evades antiviral innate immunity by inhibiting JAK1/STAT signalling

Author

Listed:
  • Hui Yang

    (Yangzhou University)

  • Yurui Dong

    (Yangzhou University)

  • Ying Bian

    (Yangzhou University)

  • Nuo Xu

    (Yangzhou University)

  • Yuwei Wu

    (Yangzhou University)

  • Fan Yang

    (Yangzhou University)

  • Yinping Du

    (Yangzhou University)

  • Tao Qin

    (Yangzhou University
    Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses
    Yangzhou University
    Jiangsu Research Centre of Engineering and Technology for Prevention and Control of Poultry Disease)

  • Sujuan Chen

    (Yangzhou University
    Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses
    Yangzhou University
    Jiangsu Research Centre of Engineering and Technology for Prevention and Control of Poultry Disease)

  • Daxin Peng

    (Yangzhou University
    Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses
    Yangzhou University
    Jiangsu Research Centre of Engineering and Technology for Prevention and Control of Poultry Disease)

  • Xiufan Liu

    (Yangzhou University
    Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonoses
    Yangzhou University
    Jiangsu Research Centre of Engineering and Technology for Prevention and Control of Poultry Disease)

Abstract

Influenza A virus (IAV) polymerase protein PB2 has been shown to partially inhibit the host immune response by blocking the induction of interferons (IFNs). However, the IAV PB2 protein that regulates the downstream signaling pathway of IFNs is not well characterized. Here, we report that IAV PB2 protein reduces cellular sensitivity to IFNs, suppressing the activation of STAT1/STAT2 and ISGs. Furthermore, IAV PB2 protein targets mammalian JAK1 at lysine 859 and 860 for ubiquitination and degradation. Notably, the H5 subtype of highly pathogenic avian influenza virus with I283M/K526R mutations on PB2 increases the ability to degrade mammalian JAK1 and exhibits higher replicate efficiency in mammalian (but not avian) cells and mouse lung tissues, and causes greater mortality in infected mice. Altogether, these data describe a negative regulatory mechanism involving PB2-JAK1 and provide insights into an evasion strategy from host antiviral immunity employed by IAV.

Suggested Citation

  • Hui Yang & Yurui Dong & Ying Bian & Nuo Xu & Yuwei Wu & Fan Yang & Yinping Du & Tao Qin & Sujuan Chen & Daxin Peng & Xiufan Liu, 2022. "The influenza virus PB2 protein evades antiviral innate immunity by inhibiting JAK1/STAT signalling," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33909-2
    DOI: 10.1038/s41467-022-33909-2
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    References listed on IDEAS

    as
    1. Takuma Yoshizumi & Takeshi Ichinohe & Osamu Sasaki & Hidenori Otera & Shun-ichiro Kawabata & Katsuyoshi Mihara & Takumi Koshiba, 2014. "Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity," Nature Communications, Nature, vol. 5(1), pages 1-14, December.
    2. Loïc Carrique & Haitian Fan & Alexander P. Walker & Jeremy R. Keown & Jane Sharps & Ecco Staller & Wendy S. Barclay & Ervin Fodor & Jonathan M. Grimes, 2020. "Host ANP32A mediates the assembly of the influenza virus replicase," Nature, Nature, vol. 587(7835), pages 638-643, November.
    3. Wenjun Song & Pui Wang & Bobo Wing-Yee Mok & Siu-Ying Lau & Xiaofeng Huang & Wai-Lan Wu & Min Zheng & Xi Wen & Shigui Yang & Yu Chen & Lanjuan Li & Kwok-Yung Yuen & Honglin Chen, 2014. "The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication," Nature Communications, Nature, vol. 5(1), pages 1-12, December.
    4. Xiaoman Liu & Fengwen Xu & Lili Ren & Fei Zhao & Yu Huang & Liang Wei & Yingying Wang & Conghui Wang & Zhangling Fan & Shan Mei & Jingdong Song & Zhendong Zhao & Shan Cen & Chen Liang & Jianwei Wang &, 2021. "MARCH8 inhibits influenza A virus infection by targeting viral M2 protein for ubiquitination-dependent degradation in lysosomes," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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