Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response.
dc.contributor.author | Rand, Ulfert | |
dc.contributor.author | Rinas, Melanie | |
dc.contributor.author | Schwerk, Johannes | |
dc.contributor.author | Nöhren, Gesa | |
dc.contributor.author | Linnes, Melanie | |
dc.contributor.author | Kröger, Andrea | |
dc.contributor.author | Flossdorf, Michael | |
dc.contributor.author | Kály-Kullai, Kristóf | |
dc.contributor.author | Hauser, Hansjörg | |
dc.contributor.author | Höfer, Thomas | |
dc.contributor.author | Köster, Mario | |
dc.date.accessioned | 2012-06-06T14:11:36Z | en |
dc.date.available | 2012-06-06T14:11:36Z | en |
dc.date.issued | 2012 | en |
dc.identifier.citation | Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response. 2012, 8:584 Mol. Syst. Biol. | en_GB |
dc.identifier.issn | 1744-4292 | en |
dc.identifier.pmid | 22617958 | en |
dc.identifier.doi | 10.1038/msb.2012.17 | en |
dc.identifier.uri | http://hdl.handle.net/10033/227674 | en |
dc.description.abstract | The cellular recognition of viruses evokes the secretion of type-I interferons (IFNs) that induce an antiviral protective state. By live-cell imaging, we show that key steps of virus-induced signal transduction, IFN-β expression, and induction of IFN-stimulated genes (ISGs) are stochastic events in individual cells. The heterogeneity in IFN production is of cellular-and not viral-origin, and temporal unpredictability of IFN-β expression is largely due to cell-intrinsic noise generated both upstream and downstream of the activation of nuclear factor-κB and IFN regulatory factor transcription factors. Subsequent ISG induction occurs as a stochastic all-or-nothing switch, where the responding cells are protected against virus replication. Mathematical modelling and experimental validation show that reliable antiviral protection in the face of multi-layered cellular stochasticity is achieved by paracrine response amplification. Achieving coherent responses through intercellular communication is likely to be a more widely used strategy by mammalian cells to cope with pervasive stochasticity in signalling and gene expression. | |
dc.language.iso | en | en |
dc.rights | Archived with thanks to Molecular systems biology | en_GB |
dc.title | Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response. | en |
dc.type | Article | en |
dc.contributor.department | 1] Department of Gene Regulation and Differentiation, Helmholtz Centre for Infection Research, Braunschweig, Germany [2] Division of Theoretical Systems Biology, German Cancer Research Center (DKFZ) and BioQuant Center, Heidelberg, Germany. | en_GB |
dc.identifier.journal | Molecular systems biology | en_GB |
refterms.dateFOA | 2018-06-12T22:58:51Z | |
html.description.abstract | The cellular recognition of viruses evokes the secretion of type-I interferons (IFNs) that induce an antiviral protective state. By live-cell imaging, we show that key steps of virus-induced signal transduction, IFN-β expression, and induction of IFN-stimulated genes (ISGs) are stochastic events in individual cells. The heterogeneity in IFN production is of cellular-and not viral-origin, and temporal unpredictability of IFN-β expression is largely due to cell-intrinsic noise generated both upstream and downstream of the activation of nuclear factor-κB and IFN regulatory factor transcription factors. Subsequent ISG induction occurs as a stochastic all-or-nothing switch, where the responding cells are protected against virus replication. Mathematical modelling and experimental validation show that reliable antiviral protection in the face of multi-layered cellular stochasticity is achieved by paracrine response amplification. Achieving coherent responses through intercellular communication is likely to be a more widely used strategy by mammalian cells to cope with pervasive stochasticity in signalling and gene expression. |