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

tetano

Editor, Senior Moderator
Nat Commun. 2018 Jun 15;9(1):2358. doi: 10.1038/s41467-018-04792-7.
[h=1]Dual-functional peptide with defective interfering genes effectively protects mice against avian and seasonal influenza.[/h] Zhao H[SUP]1,[/SUP][SUP]2[/SUP], To KKW[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Chu H[SUP]1,[/SUP][SUP]2[/SUP], Ding Q[SUP]4[/SUP], Zhao X[SUP]2[/SUP], Li C[SUP]2[/SUP], Shuai H[SUP]2[/SUP], Yuan S[SUP]1,[/SUP][SUP]2[/SUP], Zhou J[SUP]1,[/SUP][SUP]2[/SUP], Kok KH[SUP]1,[/SUP][SUP]2[/SUP], Jiang S[SUP]5,[/SUP][SUP]6[/SUP], Yuen KY[SUP]7,[/SUP][SUP]8,[/SUP][SUP]9,[/SUP][SUP]10[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.


PMID: 29907765 PMCID: PMC6004018 DOI: 10.1038/s41467-018-04792-7
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