Antagonism between viral infection and innate immunity at the single-cell level

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dc.citation.articleNumbere1011597en_US
dc.citation.issueNumber9en_US
dc.citation.journalTitlePLOS Pathogensen_US
dc.citation.volumeNumber19en_US
dc.contributor.authorGrabowski, Fredericen_US
dc.contributor.authorKochaƄczyk, Mareken_US
dc.contributor.authorKorwek, Zbigniewen_US
dc.contributor.authorCzerkies, Maciejen_US
dc.contributor.authorPrus, Wiktoren_US
dc.contributor.authorLipniacki, Tomaszen_US
dc.date.accessioned2024-05-03T15:51:11Zen_US
dc.date.available2024-05-03T15:51:11Zen_US
dc.date.issued2023en_US
dc.description.abstractWhen infected with a virus, cells may secrete interferons (IFNs) that prompt nearby cells to prepare for upcoming infection. Reciprocally, viral proteins often interfere with IFN synthesis and IFN-induced signaling. We modeled the crosstalk between the propagating virus and the innate immune response using an agent-based stochastic approach. By analyzing immunofluorescence microscopy images we observed that the mutual antagonism between the respiratory syncytial virus (RSV) and infected A549 cells leads to dichotomous responses at the single-cell level and complex spatial patterns of cell signaling states. Our analysis indicates that RSV blocks innate responses at three levels: by inhibition of IRF3 activation, inhibition of IFN synthesis, and inhibition of STAT1/2 activation. In turn, proteins coded by IFN-stimulated (STAT1/2-activated) genes inhibit the synthesis of viral RNA and viral proteins. The striking consequence of these inhibitions is a lack of coincidence of viral proteins and IFN expression within single cells. The model enables investigation of the impact of immunostimulatory defective viral particles and signaling network perturbations that could potentially facilitate containment or clearance of the viral infection.en_US
dc.identifier.citationGrabowski, F., KochaƄczyk, M., Korwek, Z., Czerkies, M., Prus, W., & Lipniacki, T. (2023). Antagonism between viral infection and innate immunity at the single-cell level. PLOS Pathogens, 19(9), e1011597. https://doi.org/10.1371/journal.ppat.1011597en_US
dc.identifier.digitaljournal-ppat-1011597en_US
dc.identifier.doihttps://doi.org/10.1371/journal.ppat.1011597en_US
dc.identifier.urihttps://hdl.handle.net/1911/115561en_US
dc.language.isoengen_US
dc.publisherPublic Library of Scienceen_US
dc.rightsExcept where otherwise noted, this work is licensed under a Creative Commons Attribution (CC BY) license. Permission to reuse, publish, or reproduce the work beyond the terms of the license or beyond the bounds of fair use or other exemptions to copyright law must be obtained from the copyright holder.en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleAntagonism between viral infection and innate immunity at the single-cell levelen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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