Title
Systematic analysis of the mechanisms of virus-triggered type I IFN signaling pathways through mathematical modeling.
Abstract
Based on biological experimental data, we developed a mathematical model of the virus-triggered signaling pathways that lead to induction of type I IFNs and systematically analyzed the mechanisms of the cellular antiviral innate immune responses, including the negative feedback regulation of ISG56 and the positive feedback regulation of IFNs. We found that the time between 5 and 48 hours after viral infection is vital for the control and/or elimination of the virus from the host cells and demonstrated that the ISG56-induced inhibition of MITA activation is stronger than the ISG56-induced inhibition of TBK1 activation. The global parameter sensitivity analysis suggests that the positive feedback regulation of IFNs is very important in the innate antiviral system. Furthermore, the robustness of the innate immune signaling network was demonstrated using a new robustness index. These results can help us understand the mechanisms of the virus-induced innate immune response at a system level and provide instruction for further biological experiments.
Year
DOI
Venue
2013
10.1109/TCBB.2013.31
IEEE/ACM Trans. Comput. Biology Bioinform.
Keywords
Field
DocType
systematic analysis,robustness,negative feedback,cellular biophysics,biological experiment,innate immune signaling network,mita activation,time 5 hour to 48 hour,cellular antiviral innate immune responses,microorganisms,innate antiviral system,proteins,mathematical model,virus-triggered type,negative feedback regulation,antiviral innate immune response,biological experimental data,physiological models,virus-induced innate immune response,simulation,positive feedback regulation,signaling pathways,mathematical modeling,viral infection,positive feedback,analytical models,tbk1 activation,virus-triggered type i ifn signaling,isg56-induced inhibition,immune system,sensitivity analysis
Virus,Biology,Negative feedback,Cell biology,Innate immune system,Positive feedback,Signal transduction,Immune system,TANK-binding kinase 1,System level
Journal
Volume
Issue
ISSN
10
3
1557-9964
Citations 
PageRank 
References 
3
0.56
5
Authors
2
Name
Order
Citations
PageRank
Wei Zhang130.90
Xiufen Zou227225.44