The Tie2-agonist Vasculotide rescues mice from influenza virus infection
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 bee...
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Nature Publishing Group
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457136/ |
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pubmed-44571362015-06-12 The Tie2-agonist Vasculotide rescues mice from influenza virus infection Sugiyama, Michael G. Armstrong, Susan M. Wang, Changsen Hwang, David Leong-Poi, Howard Advani, Andrew Advani, Suzanne Zhang, Haibo Szaszi, Katalin Tabuchi, Arata Kuebler, Wolfgang M. Van Slyke, Paul Dumont, Dan J. Lee, Warren L. Article 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. Nature Publishing Group 2015-06-05 /pmc/articles/PMC4457136/ /pubmed/26046800 http://dx.doi.org/10.1038/srep11030 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Sugiyama, Michael G. Armstrong, Susan M. Wang, Changsen Hwang, David Leong-Poi, Howard Advani, Andrew Advani, Suzanne Zhang, Haibo Szaszi, Katalin Tabuchi, Arata Kuebler, Wolfgang M. Van Slyke, Paul Dumont, Dan J. Lee, Warren L. |
| spellingShingle |
Sugiyama, Michael G. Armstrong, Susan M. Wang, Changsen Hwang, David Leong-Poi, Howard Advani, Andrew Advani, Suzanne Zhang, Haibo Szaszi, Katalin Tabuchi, Arata Kuebler, Wolfgang M. Van Slyke, Paul Dumont, Dan J. Lee, Warren L. The Tie2-agonist Vasculotide rescues mice from influenza virus infection |
| author_facet |
Sugiyama, Michael G. Armstrong, Susan M. Wang, Changsen Hwang, David Leong-Poi, Howard Advani, Andrew Advani, Suzanne Zhang, Haibo Szaszi, Katalin Tabuchi, Arata Kuebler, Wolfgang M. Van Slyke, Paul Dumont, Dan J. Lee, Warren L. |
| author_sort |
Sugiyama, Michael G. |
| title |
The Tie2-agonist Vasculotide rescues mice from influenza virus infection |
| title_short |
The Tie2-agonist Vasculotide rescues mice from influenza virus infection |
| title_full |
The Tie2-agonist Vasculotide rescues mice from influenza virus infection |
| title_fullStr |
The Tie2-agonist Vasculotide rescues mice from influenza virus infection |
| title_full_unstemmed |
The Tie2-agonist Vasculotide rescues mice from influenza virus infection |
| title_sort |
tie2-agonist vasculotide rescues mice from influenza virus infection |
| description |
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. |
| publisher |
Nature Publishing Group |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4457136/ |
| _version_ |
1613232280804786176 |