Adaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice.

2.50
Hdl Handle:
http://hdl.handle.net/10033/576865
Title:
Adaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice.
Authors:
Otte, A; Sauter, M; Daxer, M A; McHardy, A C; Klingel, K; Gabriel, G
Abstract:
During the 2009 H1N1 influenza pandemic, infection attack rates were particularly high among young individuals who suffered from pneumonia with occasional death. Moreover, previously reported determinants of mammalian adaptation and pathogenicity were not present in 2009 pandemic H1N1 influenza A viruses. Thus, it was proposed that unknown viral factors might have contributed to disease severity in humans. In this study, we performed a comparative analysis of two clinical 2009 pandemic H1N1 strains that belong to the very early and later phases of the pandemic. We identified mutations in the viral hemagglutinin (HA) and the nucleoprotein (NP) that occurred during pandemic progression and mediate increased virulence in mice. Lethal disease outcome correlated with elevated viral replication in the alveolar epithelium, increased proinflammatory cytokine and chemokine responses, pneumonia, and lymphopenia in mice. These findings show that viral mutations that have occurred during pandemic circulation among humans are associated with severe disease in mice.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
Citation:
Adaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice. 2015, 89 (14):7329-37 J. Virol.
Journal:
Journal of virology
Issue Date:
Jul-2015
URI:
http://hdl.handle.net/10033/576865
DOI:
10.1128/JVI.00665-15
PubMed ID:
25948752
Type:
Article
Language:
en
ISSN:
1098-5514
Appears in Collections:
publications of the research group bioinformatics in infection research ([BRICS] BIFO)

Full metadata record

DC FieldValue Language
dc.contributor.authorOtte, Aen
dc.contributor.authorSauter, Men
dc.contributor.authorDaxer, M Aen
dc.contributor.authorMcHardy, A Cen
dc.contributor.authorKlingel, Ken
dc.contributor.authorGabriel, Gen
dc.date.accessioned2015-09-07T12:57:46Zen
dc.date.available2015-09-07T12:57:46Zen
dc.date.issued2015-07en
dc.identifier.citationAdaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice. 2015, 89 (14):7329-37 J. Virol.en
dc.identifier.issn1098-5514en
dc.identifier.pmid25948752en
dc.identifier.doi10.1128/JVI.00665-15en
dc.identifier.urihttp://hdl.handle.net/10033/576865en
dc.description.abstractDuring the 2009 H1N1 influenza pandemic, infection attack rates were particularly high among young individuals who suffered from pneumonia with occasional death. Moreover, previously reported determinants of mammalian adaptation and pathogenicity were not present in 2009 pandemic H1N1 influenza A viruses. Thus, it was proposed that unknown viral factors might have contributed to disease severity in humans. In this study, we performed a comparative analysis of two clinical 2009 pandemic H1N1 strains that belong to the very early and later phases of the pandemic. We identified mutations in the viral hemagglutinin (HA) and the nucleoprotein (NP) that occurred during pandemic progression and mediate increased virulence in mice. Lethal disease outcome correlated with elevated viral replication in the alveolar epithelium, increased proinflammatory cytokine and chemokine responses, pneumonia, and lymphopenia in mice. These findings show that viral mutations that have occurred during pandemic circulation among humans are associated with severe disease in mice.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshCytokinesen
dc.subject.meshDisease Models, Animalen
dc.subject.meshEpithelial Cellsen
dc.subject.meshFemaleen
dc.subject.meshHemagglutinin Glycoproteins, Influenza Virusen
dc.subject.meshHistocytochemistryen
dc.subject.meshHumansen
dc.subject.meshInfluenza A Virus, H1N1 Subtypeen
dc.subject.meshInfluenza, Humanen
dc.subject.meshLymphopeniaen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshMutationen
dc.subject.meshOrthomyxoviridae Infectionsen
dc.subject.meshPneumoniaen
dc.subject.meshRNA-Binding Proteinsen
dc.subject.meshRespiratory Mucosaen
dc.subject.meshViral Core Proteinsen
dc.subject.meshVirulenceen
dc.subject.meshVirus Replicationen
dc.titleAdaptive Mutations That Occurred during Circulation in Humans of H1N1 Influenza Virus in the 2009 Pandemic Enhance Virulence in Mice.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.en
dc.identifier.journalJournal of virologyen

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