Open AccessIntegrated modeling and analysis of intracellular and intercellular mechanisms in shaping the interferon response to viral infection
Author(s) -
Chunmei Cai,
Jie Zhou,
Xiaoqiang Sun,
Tingzhe Sun,
Weidong Xie,
Jun Cui
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0186105
Subject(s) - intracellular , paracrine signalling , interferon , biology , microbiology and biotechnology , intracellular parasite , interferon gamma , viral replication , virology , immunology , cytokine , virus , genetics , receptor
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.