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An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells

Author

Listed:
  • Xiaofeng Huang

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

  • Min Zheng

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

  • Pui Wang

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

  • Bobo Wing-Yee Mok

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

  • Siwen Liu

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

  • Siu-Ying Lau

    (State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong)

  • Pin Chen

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

  • Yen-Chin Liu

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

  • Honglian Liu

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

  • Yixin Chen

    (National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University)

  • Wenjun Song

    (State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong
    College of Life Science and Technology, Jinan University)

  • Kwok-Yung Yuen

    (State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong
    College of Life Science and Technology, Jinan University)

  • Honglin Chen

    (State Key Laboratory for Emerging Infectious Diseases, The University of Hong Kong
    Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong
    National Institute of Diagnostics and Vaccine Development in Infectious Diseases, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University)

Abstract

Influenza virus utilizes host splicing machinery to process viral mRNAs expressed from both M and NS segments. Through genetic analysis and functional characterization, we here show that the NS segment of H7N9 virus contains a unique G540A substitution, located within a previously undefined exonic splicing enhancer (ESE) motif present in the NEP mRNA of influenza A viruses. G540A supports virus replication in mammalian cells while retaining replication ability in avian cells. Host splicing regulator, SF2, interacts with this ESE to regulate splicing of NEP/NS1 mRNA and G540A substitution affects SF2–ESE interaction. The NS1 protein directly interacts with SF2 in the nucleus and modulates splicing of NS mRNAs during virus replication. We demonstrate that splicing of NEP/NS1 mRNA is regulated through a cis NEP-ESE motif and suggest a unique NEP-ESE may contribute to provide H7N9 virus with the ability to both circulate efficiently in avian hosts and replicate in mammalian cells.

Suggested Citation

  • Xiaofeng Huang & Min Zheng & Pui Wang & Bobo Wing-Yee Mok & Siwen Liu & Siu-Ying Lau & Pin Chen & Yen-Chin Liu & Honglian Liu & Yixin Chen & Wenjun Song & Kwok-Yung Yuen & Honglin Chen, 2017. "An NS-segment exonic splicing enhancer regulates influenza A virus replication in mammalian cells," Nature Communications, Nature, vol. 8(1), pages 1-15, April.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14751
    DOI: 10.1038/ncomms14751
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