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Nat Commun. 2018 Jun 15;9(1):2358. doi: 10.1038/s41467-018-04792-7.
Dual-functional peptide with defective interfering genes effectively protects mice against avian and seasonal influenza.
Zhao H1,2, To KKW1,2,3, Chu H1,2, Ding Q4, Zhao X2, Li C2, Shuai H2, Yuan S1,2, Zhou J1,2, Kok KH1,2, Jiang S5,6, Yuen KY7,8,9,10.
Author information
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.
PMID: 29907765 PMCID: PMC6004018 DOI: 10.1038/s41467-018-04792-7
Free PMC Article
Dual-functional peptide with defective interfering genes effectively protects mice against avian and seasonal influenza.
Zhao H1,2, To KKW1,2,3, Chu H1,2, Ding Q4, Zhao X2, Li C2, Shuai H2, Yuan S1,2, Zhou J1,2, Kok KH1,2, Jiang S5,6, Yuen KY7,8,9,10.
Author information
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.
PMID: 29907765 PMCID: PMC6004018 DOI: 10.1038/s41467-018-04792-7
Free PMC Article