Integrated modeling and analysis of intracellular and intercellular mechanisms in shaping the interferon response to viral infection

The interferons (IFNs) responses to viral infection are heterogeneous, while the underlying mechanisms for variability among cells are still not clear. In this study, we developed a hybrid model to systematically identify the sources of IFN induction heterogeneity. The experiment-integrated simulati...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2017-10, Vol.12 (10), p.e0186105-e0186105
Main Authors: Cai, Chunmei, Zhou, Jie, Sun, Xiaoqiang, Sun, Tingzhe, Xie, Weihong, Cui, Jun
Format: Article
Language:English
Subjects:
A549 Cells
Antiviral agents
Biology and Life Sciences
Care and treatment
Cell Shape - drug effects
Computer simulation
Diagnosis
Dosage and administration
Extracellular Space - metabolism
Gene Expression Regulation - drug effects
Health aspects
HEK293 Cells
Heterogeneity
Humans
Infections
Interferon
Interferons - pharmacology
Intracellular
Intracellular Space - metabolism
Laboratories
Medical research
Medicine and Health Sciences
Models, Biological
Paracrine Communication - drug effects
Paracrine signalling
Polymerase chain reaction
Simulation
Studies
Time Factors
Transcription activation
Transcription factors
Transcription Factors - metabolism
Transcriptional Activation - drug effects
Transcriptional Activation - genetics
Vesicular Stomatitis - genetics
Vesicular Stomatitis - metabolism
Vesicular Stomatitis - pathology
Vesiculovirus - drug effects
Vesiculovirus - physiology
Viral infections
Virus diseases
Viruses
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The interferons (IFNs) responses to viral infection are heterogeneous, while the underlying mechanisms for variability among cells are still not clear. In this study, we developed a hybrid model to systematically identify the sources of IFN induction heterogeneity. The experiment-integrated simulation demonstrated that the viral dose/type, the diversity in transcriptional factors activation and the intercellular paracrine signaling could strikingly shape the heterogeneity of IFN expression. We further determined that the IFNβ and IFNλ1 induced diverse dynamics of IFN-stimulated genes (ISGs) production. Collectively, our findings revealed the intracellular and intercellular mechanisms contributing to cell-to-cell variation in IFN induction, and further demonstrated the significant effects of IFN heterogeneity on antagonizing viruses.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0186105