2.50
Hdl Handle:
http://hdl.handle.net/10033/227674
Title:
Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response.
Authors:
Rand, Ulfert; Rinas, Melanie; Schwerk, Johannes; Nöhren, Gesa; Linnes, Melanie; Kröger, Andrea ( 0000-0002-3131-6580 ) ; Flossdorf, Michael; Kály-Kullai, Kristóf; Hauser, Hansjörg; Höfer, Thomas; Köster, Mario
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.
Affiliation:
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.
Citation:
Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response. 2012, 8:584 Mol. Syst. Biol.
Journal:
Molecular systems biology
Issue Date:
2012
URI:
http://hdl.handle.net/10033/227674
DOI:
10.1038/msb.2012.17
PubMed ID:
22617958
Type:
Article
Language:
en
ISSN:
1744-4292
Appears in Collections:
Publications of Dept. Gene Regulation and Differentiation (RDIF)

Full metadata record

DC FieldValue Language
dc.contributor.authorRand, Ulferten_GB
dc.contributor.authorRinas, Melanieen_GB
dc.contributor.authorSchwerk, Johannesen_GB
dc.contributor.authorNöhren, Gesaen_GB
dc.contributor.authorLinnes, Melanieen_GB
dc.contributor.authorKröger, Andreaen_GB
dc.contributor.authorFlossdorf, Michaelen_GB
dc.contributor.authorKály-Kullai, Kristófen_GB
dc.contributor.authorHauser, Hansjörgen_GB
dc.contributor.authorHöfer, Thomasen_GB
dc.contributor.authorKöster, Marioen_GB
dc.date.accessioned2012-06-06T14:11:36Zen
dc.date.available2012-06-06T14:11:36Zen
dc.date.issued2012en
dc.identifier.citationMulti-layered stochasticity and paracrine signal propagation shape the type-I interferon response. 2012, 8:584 Mol. Syst. Biol.en_GB
dc.identifier.issn1744-4292en
dc.identifier.pmid22617958en
dc.identifier.doi10.1038/msb.2012.17en
dc.identifier.urihttp://hdl.handle.net/10033/227674en
dc.description.abstractThe 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Molecular systems biologyen_GB
dc.titleMulti-layered stochasticity and paracrine signal propagation shape the type-I interferon response.en
dc.typeArticleen
dc.contributor.department1] 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.journalMolecular systems biologyen_GB

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