2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models

<p>Abstract</p> <p>Background</p> <p>The 2009 pandemic H1N1 influenza virus emerged in swine and quickly became a major global health threat. In mouse, non human primate, and swine infection models, the pH1N1 virus efficiently replicates in the lung and induces pro-infl...

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Main Authors: Go Jennifer T, Belisle Sarah E, Tchitchek Nicolas, Tumpey Terrence M, Ma Wenjun, Richt Juergen A, Safronetz David, Feldmann Heinz, Katze Michael G
Format: Article
Language:English
Published: BMC 2012-11-01
Series:BMC Genomics
Subjects:
Online Access:http://www.biomedcentral.com/1471-2164/13/627
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author Go Jennifer T
Belisle Sarah E
Tchitchek Nicolas
Tumpey Terrence M
Ma Wenjun
Richt Juergen A
Safronetz David
Feldmann Heinz
Katze Michael G
author_facet Go Jennifer T
Belisle Sarah E
Tchitchek Nicolas
Tumpey Terrence M
Ma Wenjun
Richt Juergen A
Safronetz David
Feldmann Heinz
Katze Michael G
author_sort Go Jennifer T
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The 2009 pandemic H1N1 influenza virus emerged in swine and quickly became a major global health threat. In mouse, non human primate, and swine infection models, the pH1N1 virus efficiently replicates in the lung and induces pro-inflammatory host responses; however, whether similar or different cellular pathways were impacted by pH1N1 virus across independent infection models remains to be further defined. To address this we have performed a comparative transcriptomic analysis of acute phase responses to a single pH1N1 influenza virus, A/California/04/2009 (CA04), in the lung of mice, macaques and swine.</p> <p>Results</p> <p>Despite similarities in the clinical course, we observed differences in inflammatory molecules elicited, and the kinetics of their gene expression changes across all three species. We found genes associated with the retinoid X receptor (RXR) signaling pathway known to control pro-inflammatory and metabolic processes that were differentially regulated during infection in each species, though the heterodimeric RXR partner, pathway associated signaling molecules, and gene expression patterns varied among the three species.</p> <p>Conclusions</p> <p>By comparing transcriptional changes in the context of clinical and virological measures, we identified differences in the host transcriptional response to pH1N1 virus across independent models of acute infection. Antiviral resistance and the emergence of new influenza viruses have placed more focus on developing drugs that target the immune system. Underlying overt clinical disease are molecular events that suggest therapeutic targets identified in one host may not be appropriate in another.</p>
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spelling doaj.art-e8cb2f92e5c34309b8ae9a03478b8ee02022-12-22T03:07:41ZengBMCBMC Genomics1471-21642012-11-0113162710.1186/1471-2164-13-6272009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection modelsGo Jennifer TBelisle Sarah ETchitchek NicolasTumpey Terrence MMa WenjunRicht Juergen ASafronetz DavidFeldmann HeinzKatze Michael G<p>Abstract</p> <p>Background</p> <p>The 2009 pandemic H1N1 influenza virus emerged in swine and quickly became a major global health threat. In mouse, non human primate, and swine infection models, the pH1N1 virus efficiently replicates in the lung and induces pro-inflammatory host responses; however, whether similar or different cellular pathways were impacted by pH1N1 virus across independent infection models remains to be further defined. To address this we have performed a comparative transcriptomic analysis of acute phase responses to a single pH1N1 influenza virus, A/California/04/2009 (CA04), in the lung of mice, macaques and swine.</p> <p>Results</p> <p>Despite similarities in the clinical course, we observed differences in inflammatory molecules elicited, and the kinetics of their gene expression changes across all three species. We found genes associated with the retinoid X receptor (RXR) signaling pathway known to control pro-inflammatory and metabolic processes that were differentially regulated during infection in each species, though the heterodimeric RXR partner, pathway associated signaling molecules, and gene expression patterns varied among the three species.</p> <p>Conclusions</p> <p>By comparing transcriptional changes in the context of clinical and virological measures, we identified differences in the host transcriptional response to pH1N1 virus across independent models of acute infection. Antiviral resistance and the emergence of new influenza viruses have placed more focus on developing drugs that target the immune system. Underlying overt clinical disease are molecular events that suggest therapeutic targets identified in one host may not be appropriate in another.</p>http://www.biomedcentral.com/1471-2164/13/627Pandemic, Influenza virusGenomicsInflammationLipid metabolismGlucocorticoid receptorLXR/RXR
spellingShingle Go Jennifer T
Belisle Sarah E
Tchitchek Nicolas
Tumpey Terrence M
Ma Wenjun
Richt Juergen A
Safronetz David
Feldmann Heinz
Katze Michael G
2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models
BMC Genomics
Pandemic, Influenza virus
Genomics
Inflammation
Lipid metabolism
Glucocorticoid receptor
LXR/RXR
title 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models
title_full 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models
title_fullStr 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models
title_full_unstemmed 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models
title_short 2009 pandemic H1N1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse, macaque, and swine infection models
title_sort 2009 pandemic h1n1 influenza virus elicits similar clinical course but differential host transcriptional response in mouse macaque and swine infection models
topic Pandemic, Influenza virus
Genomics
Inflammation
Lipid metabolism
Glucocorticoid receptor
LXR/RXR
url http://www.biomedcentral.com/1471-2164/13/627
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