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The K526R substitution in viral protein PB2 enhances the effects of E627K on influenza virus replication

Author

Listed:
  • Wenjun Song

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
    The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University)

  • Pui Wang

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
    The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University)

  • Bobo Wing-Yee Mok

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong)

  • Siu-Ying Lau

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong)

  • Xiaofeng Huang

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong)

  • Wai-Lan Wu

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong)

  • Min Zheng

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong)

  • Xi Wen

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong)

  • Shigui Yang

    (The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University
    State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University)

  • Yu Chen

    (The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University
    State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University)

  • Lanjuan Li

    (The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University
    State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Zhejiang University)

  • Kwok-Yung Yuen

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
    The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University)

  • Honglin Chen

    (State Key Laboratory for Emerging Infectious Diseases, and the Research Center of Infection and Immunology, The University of Hong Kong
    The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University)

Abstract

Host-adaptive strategies, such as the E627K substitution in the PB2 protein, are critical for replication of avian influenza A viruses in mammalian hosts. Here we show that mutation PB2-K526R is present in some human H7N9 influenza isolates, in nearly 80% of H5N1 human isolates from Indonesia and, in conjunction with E627K, in almost all seasonal H3N2 viruses since 1970. Polymerase complexes containing PB2-526R derived from H7N9, H5N1 or H3N2 viruses exhibit increased polymerase activity. PB2-526R also enhances viral transcription and replication in cells. In comparison with viruses carrying 627K, H7N9 viruses carrying both 526R and 627K replicate more efficiently in mammalian (but not avian) cells and in mouse lung tissues, and cause greater body weight loss and mortality in infected mice. PB2-K526R interacts with nuclear export protein and our results suggest that it contributes to enhance replication for certain influenza virus subtypes, particularly in combination with 627K.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6509
    DOI: 10.1038/ncomms6509
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    Cited by:

    1. 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.

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