Inhibition of highly pathogenic avian influenza (HPAI) virus by a peptide derived from vFLIP through its direct destabilization of viruses

Sci Rep. 2017 Jul 7;7(1):4875. doi: 10.1038/s41598-017-04777-4.

Abstract

The antiviral activities of synthesized Kα2-helix peptide, which was derived from the viral FLICE-like inhibitor protein (vFLIP) of Kaposi's sarcoma-associated herpesvirus (KSHV), against influenza A virus (IAV) were investigated in vitro and in vivo, and mechanisms of action were suggested. In addition to the robust autophagy activity of the Kα2-helix peptide, the present study showed that treatment with the Kα2 peptide fused with the TAT peptide significantly inhibited IAV replication and transmission. Moreover, TAT-Kα2 peptide protected the mice, that were challenged with lethal doses of highly pathogenic influenza A H5N1 or H1N1 viruses. Mechanistically, we found that TAT-Kα2 peptide destabilized the viral membranes, depending on their lipid composition of the viral envelop. In addition to IAV, the Kα2 peptide inhibited infections with enveloped viruses, such as Vesicular Stomatitis Virus (VSV) and Respiratory Syncytial Virus (RSV), without cytotoxicity. These results suggest that TAT-Kα2 peptide is a potential antiviral agent for controlling emerging or re-emerging enveloped viruses, particularly diverse subtypes of IAVs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / isolation & purification
  • Antiviral Agents / metabolism*
  • Disease Models, Animal
  • Dogs
  • Influenza A virus / drug effects*
  • Influenza A virus / physiology
  • Lung / virology
  • Madin Darby Canine Kidney Cells
  • Mice, Inbred BALB C
  • Oligopeptides / isolation & purification
  • Oligopeptides / metabolism*
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / prevention & control
  • Respiratory Syncytial Viruses / drug effects
  • Respiratory Syncytial Viruses / physiology
  • Survival Analysis
  • Treatment Outcome
  • Vesiculovirus / drug effects
  • Vesiculovirus / physiology
  • Viral Load
  • Viral Proteins / metabolism*
  • Virus Internalization / drug effects
  • Virus Release / drug effects
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Oligopeptides
  • Viral Proteins
  • viral FLIP protein, Human herpesvirus 8