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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BMC
2012-11-01
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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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