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 language | English (US) |
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Article number | 190 |
Journal | BMC systems biology |
Volume | 5 |
DOIs | |
State | Published - Nov 11 2011 |
Keywords
- Comparative transcriptomics
- Host response
- Influenza infection
- Network inference
- Systems biology
ASJC Scopus subject areas
- Structural Biology
- Modeling and Simulation
- Molecular Biology
- Computer Science Applications
- Applied Mathematics