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Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion

Paquette, Stéphane G. and Banner, David and Bao Chi, Le Thi and Leόn, Alberto J. and Xu, Luoling and Ran, Longsi and Huang, Stephen S.H. and Farooqui, Amber and Kelvin, David J. and Kelvin, Alyson A. (2014) Pandemic H1N1 influenza A directly induces a robust and acute inflammatory gene signature in primary human bronchial epithelial cells downstream of membrane fusion. Virology, Vol. 448 , p. 91-103. ISSN 0042-6822. eISSN 1096-0341. Article.

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DOI: 10.1016/j.virol.2013.09.022

Abstract

Pandemic H1N1 influenza A (H1N1pdm) elicits stronger pulmonary inflammation than previously circulating seasonal H1N1 influenza A (sH1N1), yet mechanisms of inflammatory activation in respiratory epithelial cells during H1N1pdm infection are unclear. We investigated host responses to H1N1pdm/sH1N1 infection and virus entry mechanisms in primary human bronchial epithelial cells in vitro. H1N1pdm infection rapidly initiated a robust inflammatory gene signature (3 h post-infection) not elicited by sH1N1 infection. Protein secretion inhibition had no effect on gene induction. Infection with membrane fusion deficient H1N1pdm failed to induce robust inflammatory gene expression which was rescued with restoration of fusion ability, suggesting H1N1pdm directly triggered the inflammatory signature downstream of membrane fusion. Investigation of intra-virion components revealed H1N1pdm viral RNA (vRNA) triggered a stronger inflammatory phenotype than sH1N1 vRNA. Thus, our study is first to report H1N1pdm induces greater inflammatory gene expression than sH1N1 in vitro due to direct virus–epithelial cell interaction.

Item Type:Article
ID Code:9863
Status:Published
Refereed:Yes
Uncontrolled Keywords:Influenza; Inflammation, membrane fusion, virus entry, epithelial cells, inflammatory cytokines, pandemic H1N1
Subjects:Area 06 - Scienze mediche > MED/07 Microbiologia e microbiologia clinica
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Academic Press / Elsevier
ISSN:0042-6822
eISSN:1096-0341
Copyright Holders:© 2013 The Authors. Published by Elsevier Inc. All rights reserved
Deposited On:10 Jun 2014 12:00

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