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Sci Rep. 2015 Jun 5;5:11030. doi: 10.1038/srep11030.

The Tie2-agonist Vasculotide rescues mice from influenza virus infection.

Author information

1
1] Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON [2] Department of Laboratory Medicine and Pathobiology, University of Toronto.
2
Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON.
3
1] Department of Laboratory Medicine and Pathobiology, University of Toronto [2] Department of Pathology, Toronto General Hospital, University Health Network, Toronto, ON.
4
Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, ON.
5
1] Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON [2] Department of Laboratory Medicine and Pathobiology, University of Toronto [3] Interdepartmental Division of Critical Care and Department of Medicine, University of Toronto.

Abstract

Seasonal influenza virus infections cause hundreds of thousands of deaths annually while viral mutation raises the threat of a novel pandemic strain. Antiviral drugs exhibit limited efficacy unless administered early and may induce viral resistance. Thus, targeting the host response directly has been proposed as a novel therapeutic strategy with the added potential benefit of not eliciting viral resistance. Severe influenza virus infections are complicated by respiratory failure due to the development of lung microvascular leak and acute lung injury. We hypothesized that enhancing lung endothelial barrier integrity could improve the outcome. Here we demonstrate that the Tie2-agonist tetrameric peptide Vasculotide improves survival in murine models of severe influenza, even if administered as late as 72 hours after infection; the benefit was observed using three strains of the virus and two strains of mice. The effect required Tie2, was independent of viral replication and did not impair lung neutrophil recruitment. Administration of the drug decreased lung edema, arterial hypoxemia and lung endothelial apoptosis; importantly, Vasculotide is inexpensive to produce, is chemically stable and is unrelated to any Tie2 ligands. Thus, Vasculotide may represent a novel and practical therapy for severe infections with influenza.

PMID:
26046800
PMCID:
PMC4457136
DOI:
10.1038/srep11030
[Indexed for MEDLINE]
Free PMC Article

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