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Dual-functional peptide with defective interfering genes effectively protects mice against avian and seasonal influenza

Author

Listed:
  • Hanjun Zhao

    (The University of Hong Kong
    The University of Hong Kong)

  • Kelvin K. W. To

    (The University of Hong Kong
    The University of Hong Kong
    The University of Hong Kong)

  • Hin Chu

    (The University of Hong Kong
    The University of Hong Kong)

  • Qiulu Ding

    (The University of Hong Kong)

  • Xiaoyu Zhao

    (The University of Hong Kong)

  • Cun Li

    (The University of Hong Kong)

  • Huiping Shuai

    (The University of Hong Kong)

  • Shuofeng Yuan

    (The University of Hong Kong
    The University of Hong Kong)

  • Jie Zhou

    (The University of Hong Kong
    The University of Hong Kong)

  • Kin-Hang Kok

    (The University of Hong Kong
    The University of Hong Kong)

  • Shibo Jiang

    (Fudan University
    New York Blood Center)

  • Kwok-Yung Yuen

    (The University of Hong Kong
    The University of Hong Kong
    The University of Hong Kong
    The University of Hong Kong)

Abstract

Limited efficacy of current antivirals and antiviral-resistant mutations impairs anti-influenza treatment. Here, we evaluate the in vitro and in vivo antiviral effect of three defective interfering genes (DIG-3) of influenza virus. Viral replication is significantly reduced in cell lines transfected with DIG-3. Mice treated with DIG-3 encoded by jetPEI-vector, as prophylaxis and therapeutics against A(H7N7) virus, respectively, have significantly better survivals (80% and 50%) than control mice (0%). We further develop a dual-functional peptide TAT-P1, which delivers DIG-3 with high efficiency and concomitantly exerts antiviral activity by preventing endosomal acidification. TAT-P1/DIG-3 is more effective than jetPEI/DIG-3 in treating A(H7N7) or A(H1N1)pdm09-infected mice and shows potent prophylactic protection on A(H7N7) or A(H1N1)pdm09-infected mice. The addition of P1 peptide, which prevents endosomal acidification, can enhance the protection of TAT-P1/DIG-3 on A(H1N1)pdm09-infected mice. Dual-functional TAT-P1 with DIG-3 can effectively protect or treat mice infected by avian and seasonal influenza virus.

Suggested Citation

  • Hanjun Zhao & Kelvin K. W. To & Hin Chu & Qiulu Ding & Xiaoyu Zhao & Cun Li & Huiping Shuai & Shuofeng Yuan & Jie Zhou & Kin-Hang Kok & Shibo Jiang & Kwok-Yung Yuen, 2018. "Dual-functional peptide with defective interfering genes effectively protects mice against avian and seasonal influenza," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04792-7
    DOI: 10.1038/s41467-018-04792-7
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