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

dc.citation.articleNumbere1011597
dc.citation.issueNumber9
dc.citation.journalTitlePLOS Pathogens
dc.citation.volumeNumber19
dc.contributor.authorGrabowski, Frederic
dc.contributor.authorKochaƄczyk, Marek
dc.contributor.authorKorwek, Zbigniew
dc.contributor.authorCzerkies, Maciej
dc.contributor.authorPrus, Wiktor
dc.contributor.authorLipniacki, Tomasz
dc.date.accessioned2024-05-03T15:51:11Z
dc.date.available2024-05-03T15:51:11Z
dc.date.issued2023
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.
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.1011597
dc.identifier.digitaljournal-ppat-1011597
dc.identifier.doihttps://doi.org/10.1371/journal.ppat.1011597
dc.identifier.urihttps://hdl.handle.net/1911/115561
dc.language.isoeng
dc.publisherPublic Library of Science
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.
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleAntagonism between viral infection and innate immunity at the single-cell level
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
Files
Original bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
journal-ppat-1011597.pdf
Size:
4.79 MB
Format:
Adobe Portable Document Format