Cited by 142Influenza Virus Research Studiesinterferon and immune responsesVirology and Viral Diseases

Lethal Dissemination of H5N1 Influenza Virus Is Associated with Dysregulation of Inflammation and Lipoxin Signaling in a Mouse Model of Infection

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Cilloniz, Cristian, Pantin-Jackwood, Mary J., Ni, Chester, Goodman, Alan G., Peng, Xinxia, Proll, Sean C., Carter, Victoria S., Rosenzweig, Elizabeth R. +6 more·2010·Journal of Virology

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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  • Cytokine signaling pathway redundancy is also observed with respect to type I IFN signaling, as there is strong upregulation of IFN-stimulated gene expression in IFN-alpha/betaR KO mice infected with the 1918 virus.

    “Cytokine signaling pathway redundancy is also observed with respect to type I IFN signaling, as there is strong upregulation of IFN-stimulated gene expression in IFN-␣/␤R KO mice infected with the 1918 virus (27).”

    From Into the Eye of the Cytokine Storm (2012) · cites this paper as [27]

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Authors
Cilloniz, C., Pantin-Jackwood, M. J., Ni, C., Goodman, A. G., Peng, X., Proll, S. C., Carter, V. S., Rosenzweig, E. R., Szretter, K. J., Katz, J. M., Korth, M. J., Swayne, D. E., Tumpey, T. M., & Katze, M. G.
Affiliations
  • Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195
  • Southeast Poultry Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, Athens, Georgia 30606
  • University of Washington (US)
  • Washington University in St. Louis (US)
  • Centers for Disease Control and Prevention (US)
  • Agricultural Research Service (US)
Corresponding author
Katze, Michael G.
Venue
Journal of Virology
Published
2010-08
Volume
84
Issue
15
Pages
7613-7624
ISSN
  • 0022-538X (ISSN-L)
  • 1098-5514
OpenAlex
W2130014663
Cited by
136
References
49
Citations by year
2026: 2 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 6 · 2021: 10 · 2020: 13 · 2019: 4 · 2018: 5 · 2017: 7 · 2016: 5 · 2015: 14 · 2014: 8 · 2013: 14 · 2012: 10
FWCI
10.97
Type
journal article
Language
en
Open access
Locations
  • Journal of Virology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Allergy and Infectious Diseases (P01AI058113)
Topics
  • Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
H5N1 influenza virus, influenza pathogenesis, lung gene expression, inflammation, inflammasome, type I interferon, interferon receptor, viral dissemination, extrapulmonary infection, brain infection, host transcriptional response
MeSH terms
Animals, Female, Gene Expression Regulation, Inflammation, Lung, Orthomyxoviridae Infections, Virulence, Signal Transduction, Survival Analysis, Lipoxins, Mice, Influenza A Virus, H1N1 Subtype, Influenza A Virus, H5N1 Subtype

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