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ID 114996
Title Alternative
Vascular hyperpermeability in severe influenza
Author
Hiyoshi, Mineyoshi The University of Tokushima|Shimane University
Indalao, I. L. The University of Tokushima
Yano, Mihiro The University of Tokushima|The University of Shiga Prefecture
Yamane, Kazuhiko The University of Tokushima
Content Type
Journal Article
Description
Multiorgan failure with vascular hyperpermeability is the final outcome in the progression of seasonal influenza virus pneumonia and influenza-associated encephalopathy, and it is also common in infection with highly pathogenic avian influenza virus. However, the precise molecular mechanism by which influenza virus infection causes vascular endothelial cell hyperpermeability remains poorly defined. We investigated the mechanisms of hyperpermeability of human umbilical vein endothelial cells infected with influenza A virus (IAV)/Puerto Rico/8/34 (PR8) (H1N1). The levels of β-catenin, a key regulatory component of the vascular endothelial-cadherin cell adhesion complex, were markedly decreased during infection for 28 h, with increments of vascular hyperpermeability measured by transendothelial electrical resistance. Lactacystin (at 2 μM), a proteasome inhibitor, inhibited the decrease in β-catenin levels. Since the N-terminal phosphorylation of β-catenin by glycogen synthase kinase (GSK)-3β is the initiation step of proteasome-dependent degradation, we examined the effects of GSK-3β suppression by RNA interference in endothelial cells. IAV-infection-induced β-catenin degradation was significantly inhibited in GSK-3β-knockdown cells, and transfection of cells with recombinant β-catenin significantly suppressed IAV-induced hyperpermeability. These findings suggest that IAV infection induces GSK-3β-mediated β-catenin degradation in the adherens junctional complexes and induces vascular hyperpermeability. The in vitro findings of β-catenin degradation and activation of GSK-3β after IAV infection were confirmed in lungs of mice infected with IAV PR8 during the course of infection from day 0 to day 6. These results suggest that GSK-3β-mediated β-catenin degradation in adherens junctions is one of the key mechanisms of vascular hyperpermeability in severe influenza.
Journal Title
Archives of Virology
ISSN
03048608
14328798
NCID
AA00548901
Publisher
Springer Nature
Volume
160
Issue
1
Start Page
225
End Page
234
Published Date
2014-11-12
Rights
This article is distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/) which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
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DOI (Published Version)
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language
eng
TextVersion
Publisher
departments
Institute of Advanced Medical Sciences