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

Hanjun Zhao1,2, Kelvin K W To1,2,3, Hin Chu1,2

  • 1State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.

Nature Communications
|June 17, 2018
PubMed

Insights

New defective interfering genes (DIG-3) show potent antiviral activity against influenza viruses. A dual-functional peptide enhances DIG-3 delivery and efficacy, offering promising protection for seasonal and avian influenza infections.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • Current influenza antivirals have limited efficacy and are challenged by drug-resistant mutations.
  • Influenza virus poses a significant threat to public health, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To evaluate the antiviral effects of defective interfering genes (DIG-3) against influenza virus in vitro and in vivo.
  • To develop and assess a dual-functional peptide (TAT-P1) for enhanced delivery and activity of DIG-3.

Main Methods:

  • In vitro assessment of DIG-3 on viral replication in cell lines.
  • In vivo studies using jetPEI-vector and TAT-P1/DIG-3 in mice infected with influenza A (H7N7) and A (H1N1)pdm09 viruses.
  • Evaluation of prophylactic and therapeutic effects of the developed treatments.

Main Results:

  • DIG-3 significantly reduced viral replication in cell lines.
  • Mice treated with DIG-3/jetPEI showed improved survival rates against A(H7N7) infection.
  • TAT-P1/DIG-3 demonstrated superior efficacy compared to jetPEI/DIG-3 in treating and preventing infections by A(H7N7) and A(H1N1)pdm09 viruses.
  • The P1 peptide's ability to prevent endosomal acidification enhanced TAT-P1/DIG-3's protective effects.

Conclusions:

  • Defective interfering genes (DIG-3) represent a potent antiviral strategy against influenza viruses.
  • The dual-functional peptide TAT-P1 enhances DIG-3 delivery and antiviral activity, offering a promising therapeutic approach.
  • TAT-P1/DIG-3 provides effective protection and treatment for both avian and seasonal influenza infections in vivo.

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