Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.

Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA)...

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Autores principales:	Bastian Hatesuer, Stephanie Bertram, Nora Mehnert, Mahmoud M Bahgat, Peter S Nelson, Stefan Pöhlmann, Klaus Schughart
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7cdc567aa0b24c34ae5832e23347ce0d
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spelling	oai:doaj.org-article:7cdc567aa0b24c34ae5832e23347ce0d2021-11-18T06:07:16ZTmprss2 is essential for influenza H1N1 virus pathogenesis in mice.1553-73661553-737410.1371/journal.ppat.1003774https://doaj.org/article/7cdc567aa0b24c34ae5832e23347ce0d2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24348248/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. However, it is unknown which proteases activate influenza viruses in mammals. Several candidates have been identified in cell culture studies, leading to the concept that influenza viruses can employ multiple enzymes to ensure their cleavage activation in the host. Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic 2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice were protected from weight loss, death and impairment of lung function. Also, after infection with mono-basic H3N2 influenza A virus body weight loss and survival was less severe in Tmprss2 mutant compared to wild type mice. As expected, Tmprss2-deficient mice were not protected from viral spread and pathology after infection with multi-basic H7N7 influenza A virus. In conclusion, these results identify TMPRSS2 as a host cell factor essential for viral spread and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses.Bastian HatesuerStephanie BertramNora MehnertMahmoud M BahgatPeter S NelsonStefan PöhlmannKlaus SchughartPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 12, p e1003774 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Bastian Hatesuer Stephanie Bertram Nora Mehnert Mahmoud M Bahgat Peter S Nelson Stefan Pöhlmann Klaus Schughart Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.
description	Annual influenza epidemics and occasional pandemics pose a severe threat to human health. Host cell factors required for viral spread but not for cellular survival are attractive targets for novel approaches to antiviral intervention. The cleavage activation of the influenza virus hemagglutinin (HA) by host cell proteases is essential for viral infectivity. However, it is unknown which proteases activate influenza viruses in mammals. Several candidates have been identified in cell culture studies, leading to the concept that influenza viruses can employ multiple enzymes to ensure their cleavage activation in the host. Here, we show that deletion of a single HA-activating protease gene, Tmprss2, in mice inhibits spread of mono-basic H1N1 influenza viruses, including the pandemic 2009 swine influenza virus. Lung pathology was strongly reduced and mutant mice were protected from weight loss, death and impairment of lung function. Also, after infection with mono-basic H3N2 influenza A virus body weight loss and survival was less severe in Tmprss2 mutant compared to wild type mice. As expected, Tmprss2-deficient mice were not protected from viral spread and pathology after infection with multi-basic H7N7 influenza A virus. In conclusion, these results identify TMPRSS2 as a host cell factor essential for viral spread and pathogenesis of mono-basic H1N1 and H3N2 influenza A viruses.
format	article
author	Bastian Hatesuer Stephanie Bertram Nora Mehnert Mahmoud M Bahgat Peter S Nelson Stefan Pöhlmann Klaus Schughart
author_facet	Bastian Hatesuer Stephanie Bertram Nora Mehnert Mahmoud M Bahgat Peter S Nelson Stefan Pöhlmann Klaus Schughart
author_sort	Bastian Hatesuer
title	Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.
title_short	Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.
title_full	Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.
title_fullStr	Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.
title_full_unstemmed	Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.
title_sort	tmprss2 is essential for influenza h1n1 virus pathogenesis in mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7cdc567aa0b24c34ae5832e23347ce0d
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Tmprss2 is essential for influenza H1N1 virus pathogenesis in mice.

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