Journal article
Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection
Journal of virology, Vol.84(15), pp.7613-7624
08/2010
Handle:
https://hdl.handle.net/2376/113665
PMCID: PMC2897611
PMID: 20504916
Abstract
Periodic outbreaks of highly pathogenic avian H5N1 influenza viruses and the current H1N1 pandemic highlight the need for a more detailed understanding of influenza virus pathogenesis. To investigate the host transcriptional response induced by pathogenic influenza viruses, we used a functional-genomics approach to compare gene expression profiles in lungs from 129S6/SvEv mice infected with either the fully reconstructed H1N1 1918 pandemic virus (1918) or the highly pathogenic avian H5N1 virus Vietnam/1203/04 (VN/1203). Although the viruses reached similar titers in the lung and caused lethal infections, the mean time of death was 6 days for VN/1203-infected animals and 9 days for mice infected with the 1918 virus. VN/1203-infected animals also exhibited an earlier and more potent inflammatory response. This response included induction of genes encoding components of the inflammasome. VN/1203 was also able to disseminate to multiple organs, including the brain, which correlated with changes in the expression of genes associated with hematological functions and lipoxin biogenesis and signaling. Both viruses elicited expression of type I interferon (IFN)-regulated genes in wild-type mice and to a lesser extent in mice lacking the type I IFN receptor, suggesting alternative or redundant pathways for IFN signaling. Our findings suggest that VN/1203 is more pathogenic in mice as a consequence of several factors, including the early and sustained induction of the inflammatory response, the additive or synergistic effects of upregulated components of the immune response, and inhibition of lipoxin-mediated anti-inflammatory responses, which correlated with the ability of VN/1203 to disseminate to extrapulmonary organs.
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Details
- Title
- Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection
- Creators
- Cristian Cilloniz - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Mary J Pantin-Jackwood - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Chester Ni - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Alan G Goodman - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Xinxia Peng - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Sean C Proll - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Victoria S Carter - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Elizabeth R Rosenzweig - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Kristy J Szretter - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Jacqueline M Katz - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Marcus J Korth - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195David E Swayne - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Terrence M Tumpey - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195Michael G Katze - Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195
- Publication Details
- Journal of virology, Vol.84(15), pp.7613-7624
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- American Society for Microbiology (ASM)
- Identifiers
- 99900547987601842
- Language
- English
- Resource Type
- Journal article