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

Journal Article · · BMC Systems Biology
 [1];  [1];  [2];  [3];  [2];  [2];  [4];  [5];  [6];  [7];  [1]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States). Computational Biology and Bioinformatics Groups
  2. Univ. of Wisconsin, Madison, WI (United States). Influenza Research Inst., Dept. of Pathobiological Sciences
  3. Univ. of Washington, Seattle, WA (United States). Dept. of Microbiology
  4. Oregon Health and Science Univ., Portland, OR (United States). Dept. of Public Health and Preventive Medicine and Knight Cancer Inst.
  5. Battelle, Columbus, OH (United States)
  6. Univ. of Wisconsin, Madison, WI (United States). Influenza Research Inst., Dept. of Pathobiological Sciences; Univ. of Tokyo (Japan); ERATO, Saitama (Japan)
  7. Univ. of Washington, Seattle, WA (United States). Dept. of Microbiology and Washington National Primate Research Center
+ Show Author Affiliations

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.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID)
Grant/Contract Number:
AC05-76RL01830; HHSN272200800060C
OSTI ID:
1626646
Journal Information:
BMC Systems Biology, Vol. 5, Issue 1; ISSN 1752-0509
Publisher:
BioMed CentralCopyright Statement
Country of Publication:
United States
Language:
English

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C57BL/6J and C57BL/6NJ Mice Are Differentially Susceptible to Inflammation-Associated Disease Caused by Influenza A Virus journal January 2019
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Host Response Comparison of H1N1- and H5N1-Infected Mice Identifies Two Potential Death Mechanisms journal July 2017

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Related Subjects

97 MATHEMATICS AND COMPUTING
59 BASIC BIOLOGICAL SCIENCES
mathematical & computational biology
systems biology
influenza infection
host response
network inference
comparative transcriptomics