Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems

Jason E. McDermott, Harish Shankaran, Amie J. Eisfeld, Sarah E. Belisle, Gabriele Neuman, Chengjun Li, Shannon McWeeney, Carol Sabourin, Yoshihiro Kawaoka, Michael G. Katze, Katrina M. Waters

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background: Understanding host response to influenza virus infection will facilitate development of better diagnoses and therapeutic interventions. Several different experimental models have been used as a proxy for human infection, including cell cultures derived from human cells, mice, and non-human primates. Each of these systems has been studied extensively in isolation, but little effort has been directed toward systematically characterizing the conservation of host response on a global level beyond known immune signaling cascades.Results: In the present study, we employed a multivariate modeling approach to characterize and compare the transcriptional regulatory networks between these three model systems after infection with a highly pathogenic avian influenza virus of the H5N1 subtype. Using this approach we identified functions and pathways that display similar behavior and/or regulation including the well-studied impact on the interferon response and the inflammasome. Our results also suggest a primary response role for airway epithelial cells in initiating hypercytokinemia, which is thought to contribute to the pathogenesis of H5N1 viruses. We further demonstrate that we can use a transcriptional regulatory model from the human cell culture data to make highly accurate predictions about the behavior of important components of the innate immune system in tissues from whole organisms.Conclusions: This is the first demonstration of a global regulatory network modeling conserved host response between in vitro and in vivo models.

Original languageEnglish (US)
Article number190
JournalBMC Systems Biology
Volume5
DOIs
StatePublished - Nov 11 2011

Fingerprint

Cell Culture
Influenza in Birds
Influenza
Macaca
Virus Diseases
Orthomyxoviridae
Viruses
Cell culture
Virus
Infection
Mouse
Cell Culture Techniques
Inflammasomes
Regulatory Networks
H5N1 Subtype Influenza A Virus
Gene Regulatory Networks
Proxy
Interferons
Primates
Immune system

Keywords

  • Comparative transcriptomics
  • Host response
  • Influenza infection
  • Network inference
  • Systems biology

ASJC Scopus subject areas

  • Molecular Biology
  • Structural Biology
  • Applied Mathematics
  • Modeling and Simulation
  • Computer Science Applications

Cite this

Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems. / McDermott, Jason E.; Shankaran, Harish; Eisfeld, Amie J.; Belisle, Sarah E.; Neuman, Gabriele; Li, Chengjun; McWeeney, Shannon; Sabourin, Carol; Kawaoka, Yoshihiro; Katze, Michael G.; Waters, Katrina M.

In: BMC Systems Biology, Vol. 5, 190, 11.11.2011.

Research output: Contribution to journalArticle

McDermott, JE, Shankaran, H, Eisfeld, AJ, Belisle, SE, Neuman, G, Li, C, McWeeney, S, Sabourin, C, Kawaoka, Y, Katze, MG & Waters, KM 2011, 'Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems', BMC Systems Biology, vol. 5, 190. https://doi.org/10.1186/1752-0509-5-190
McDermott, Jason E. ; Shankaran, Harish ; Eisfeld, Amie J. ; Belisle, Sarah E. ; Neuman, Gabriele ; Li, Chengjun ; McWeeney, Shannon ; Sabourin, Carol ; Kawaoka, Yoshihiro ; Katze, Michael G. ; Waters, Katrina M. / Conserved host response to highly pathogenic avian influenza virus infection in human cell culture, mouse and macaque model systems. In: BMC Systems Biology. 2011 ; Vol. 5.
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