Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses

ABSTRACT Secondary bacterial infections increase disease severity of influenza virus infections and contribute greatly to increased morbidity and mortality during pandemics. To study secondary bacterial infection following influenza virus infection, mice were inoculated with sublethal doses of 2009...

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Autores principales:	John C. Kash, Kathie-Anne Walters, A. Sally Davis, Aline Sandouk, Louis M. Schwartzman, Brett W. Jagger, Daniel S. Chertow, Li Qi, Rolf E. Kuestner, Adrian Ozinsky, Jeffery K. Taubenberger
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b60597ee78454a638166901323a25cac
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spelling	oai:doaj.org-article:b60597ee78454a638166901323a25cac2021-11-15T15:38:58ZLethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses10.1128/mBio.00172-112150-7511https://doaj.org/article/b60597ee78454a638166901323a25cac2011-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00172-11https://doaj.org/toc/2150-7511ABSTRACT Secondary bacterial infections increase disease severity of influenza virus infections and contribute greatly to increased morbidity and mortality during pandemics. To study secondary bacterial infection following influenza virus infection, mice were inoculated with sublethal doses of 2009 seasonal H1N1 virus (NIH50) or pandemic H1N1 virus (Mex09) followed by inoculation with Streptococcus pneumoniae 48 h later. Disease was characterized by assessment of weight loss and survival, titration of virus and bacteria by quantitative reverse transcription-PCR (qRT-PCR), histopathology, expression microarray, and immunohistochemistry. Mice inoculated with virus alone showed 100% survival for all groups. Mice inoculated with Mex09 plus S. pneumoniae showed severe weight loss and 100% mortality with severe alveolitis, denuded bronchiolar epithelium, and widespread expression of apoptosis marker cleaved caspase 3. In contrast, mice inoculated with NIH50 plus S. pneumoniae showed increased weight loss, 100% survival, and slightly enhanced lung pathology. Mex09-S. pneumoniae coinfection also resulted in increased S. pneumoniae replication in lung and bacteremia late in infection. Global gene expression profiling revealed that Mex09-S. pneumoniae coinfection did not induce significantly more severe inflammatory responses but featured significant loss of epithelial cell reproliferation and repair responses. Histopathological examination for cell proliferation marker MCM7 showed significant staining of airway epithelial cells in all groups except Mex09-S. pneumoniae-infected mice. This study demonstrates that secondary bacterial infection during 2009 H1N1 pandemic virus infection resulted in more severe disease and loss of lung repair responses than did seasonal influenza viral and bacterial coinfection. Moreover, this study provides novel insights into influenza virus and bacterial coinfection by showing correlation of lethal outcome with loss of airway basal epithelial cells and associated lung repair responses. IMPORTANCE Secondary bacterial pneumonias lead to increased disease severity and have resulted in a significant percentage of deaths during influenza pandemics. To understand the biological basis for the interaction of bacterial and viral infections, mice were infected with sublethal doses of 2009 seasonal H1N1 and pandemic H1N1 viruses followed by infection with Streptococcus pneumoniae 48 h later. Only infection with 2009 pandemic H1N1 virus and S. pneumoniae resulted in severe disease with a 100% fatality rate. Analysis of the host response to infection during lethal coinfection showed a significant loss of responses associated with lung repair that was not observed in any of the other experimental groups. This group of mice also showed enhanced bacterial replication in the lung. This study reveals that the extent of lung damage during viral infection influences the severity of secondary bacterial infections and may help explain some differences in mortality during influenza pandemics.John C. KashKathie-Anne WaltersA. Sally DavisAline SandoukLouis M. SchwartzmanBrett W. JaggerDaniel S. ChertowLi QiRolf E. KuestnerAdrian OzinskyJeffery K. TaubenbergerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 5 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 John C. Kash Kathie-Anne Walters A. Sally Davis Aline Sandouk Louis M. Schwartzman Brett W. Jagger Daniel S. Chertow Li Qi Rolf E. Kuestner Adrian Ozinsky Jeffery K. Taubenberger Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses
description	ABSTRACT Secondary bacterial infections increase disease severity of influenza virus infections and contribute greatly to increased morbidity and mortality during pandemics. To study secondary bacterial infection following influenza virus infection, mice were inoculated with sublethal doses of 2009 seasonal H1N1 virus (NIH50) or pandemic H1N1 virus (Mex09) followed by inoculation with Streptococcus pneumoniae 48 h later. Disease was characterized by assessment of weight loss and survival, titration of virus and bacteria by quantitative reverse transcription-PCR (qRT-PCR), histopathology, expression microarray, and immunohistochemistry. Mice inoculated with virus alone showed 100% survival for all groups. Mice inoculated with Mex09 plus S. pneumoniae showed severe weight loss and 100% mortality with severe alveolitis, denuded bronchiolar epithelium, and widespread expression of apoptosis marker cleaved caspase 3. In contrast, mice inoculated with NIH50 plus S. pneumoniae showed increased weight loss, 100% survival, and slightly enhanced lung pathology. Mex09-S. pneumoniae coinfection also resulted in increased S. pneumoniae replication in lung and bacteremia late in infection. Global gene expression profiling revealed that Mex09-S. pneumoniae coinfection did not induce significantly more severe inflammatory responses but featured significant loss of epithelial cell reproliferation and repair responses. Histopathological examination for cell proliferation marker MCM7 showed significant staining of airway epithelial cells in all groups except Mex09-S. pneumoniae-infected mice. This study demonstrates that secondary bacterial infection during 2009 H1N1 pandemic virus infection resulted in more severe disease and loss of lung repair responses than did seasonal influenza viral and bacterial coinfection. Moreover, this study provides novel insights into influenza virus and bacterial coinfection by showing correlation of lethal outcome with loss of airway basal epithelial cells and associated lung repair responses. IMPORTANCE Secondary bacterial pneumonias lead to increased disease severity and have resulted in a significant percentage of deaths during influenza pandemics. To understand the biological basis for the interaction of bacterial and viral infections, mice were infected with sublethal doses of 2009 seasonal H1N1 and pandemic H1N1 viruses followed by infection with Streptococcus pneumoniae 48 h later. Only infection with 2009 pandemic H1N1 virus and S. pneumoniae resulted in severe disease with a 100% fatality rate. Analysis of the host response to infection during lethal coinfection showed a significant loss of responses associated with lung repair that was not observed in any of the other experimental groups. This group of mice also showed enhanced bacterial replication in the lung. This study reveals that the extent of lung damage during viral infection influences the severity of secondary bacterial infections and may help explain some differences in mortality during influenza pandemics.
format	article
author	John C. Kash Kathie-Anne Walters A. Sally Davis Aline Sandouk Louis M. Schwartzman Brett W. Jagger Daniel S. Chertow Li Qi Rolf E. Kuestner Adrian Ozinsky Jeffery K. Taubenberger
author_facet	John C. Kash Kathie-Anne Walters A. Sally Davis Aline Sandouk Louis M. Schwartzman Brett W. Jagger Daniel S. Chertow Li Qi Rolf E. Kuestner Adrian Ozinsky Jeffery K. Taubenberger
author_sort	John C. Kash
title	Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_short	Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_full	Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_fullStr	Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_full_unstemmed	Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses
title_sort	lethal synergism of 2009 pandemic h1n1 influenza virus and <named-content content-type="genus-species">streptococcus pneumoniae</named-content> coinfection is associated with loss of murine lung repair responses
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/b60597ee78454a638166901323a25cac
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Lethal Synergism of 2009 Pandemic H1N1 Influenza Virus and <named-content content-type="genus-species">Streptococcus pneumoniae</named-content> Coinfection Is Associated with Loss of Murine Lung Repair Responses

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