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Modeling and Dynamical Analysis of Virus-Triggered Innate Immune Signaling Pathways

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  • Jinying Tan
  • Ruangang Pan
  • Lei Qiao
  • Xiufen Zou
  • Zishu Pan

Abstract

The investigation of the dynamics and regulation of virus-triggered innate immune signaling pathways at a system level will enable comprehensive analysis of the complex interactions that maintain the delicate balance between resistance to infection and viral disease. In this study, we developed a delayed mathematical model to describe the virus-induced interferon (IFN) signaling process by considering several key players in the innate immune response. Using dynamic analysis and numerical simulation, we evaluated the following predictions regarding the antiviral responses: (1) When the replication ratio of virus is less than 1, the infectious virus will be eliminated by the immune system’s defenses regardless of how the time delays are changed. (2) The IFN positive feedback regulation enhances the stability of the innate immune response and causes the immune system to present the bistability phenomenon. (3) The appropriate duration of viral replication and IFN feedback processes stabilizes the innate immune response. The predictions from the model were confirmed by monitoring the virus titer and IFN expression in infected cells. The results suggest that the balance between viral replication and IFN-induced feedback regulation coordinates the dynamical behavior of virus-triggered signaling and antiviral responses. This work will help clarify the mechanisms of the virus-induced innate immune response at a system level and provide instruction for further biological experiments.

Suggested Citation

  • Jinying Tan & Ruangang Pan & Lei Qiao & Xiufen Zou & Zishu Pan, 2012. "Modeling and Dynamical Analysis of Virus-Triggered Innate Immune Signaling Pathways," PLOS ONE, Public Library of Science, vol. 7(10), pages 1-15, October.
    • Handle: RePEc:plo:pone00:0048114
    DOI: 10.1371/journal.pone.0048114
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    References listed on IDEAS

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    1. Ruslan Medzhitov, 2007. "Recognition of microorganisms and activation of the immune response," Nature, Nature, vol. 449(7164), pages 819-826, October.
    2. Luis Mier-y-Terán-Romero & Mary Silber & Vassily Hatzimanikatis, 2010. "The Origins of Time-Delay in Template Biopolymerization Processes," PLOS Computational Biology, Public Library of Science, vol. 6(4), pages 1-15, April.
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    Cited by:

    1. Bianca Schmid & Melanie Rinas & Alessia Ruggieri & Eliana Gisela Acosta & Marie Bartenschlager & Antje Reuter & Wolfgang Fischl & Nathalie Harder & Jan-Philip Bergeest & Michael Flossdorf & Karl Rohr , 2015. "Live Cell Analysis and Mathematical Modeling Identify Determinants of Attenuation of Dengue Virus 2’-O-Methylation Mutant," PLOS Pathogens, Public Library of Science, vol. 11(12), pages 1-36, December.

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