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

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 and Kwok-Yung Yuen ()
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Hanjun Zhao: The University of Hong Kong
Kelvin K. W. To: The University of Hong Kong
Hin Chu: 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
Jie Zhou: The University of Hong Kong
Kin-Hang Kok: The University of Hong Kong
Shibo Jiang: Fudan University
Kwok-Yung Yuen: The University of Hong Kong

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-04792-7

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