Cellular state landscape and herpes simplex virus type 1 infection progression are connected

Abstract Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of this heterogeneity has yet to be clarified. To study the multimodal response of single human cells to herpes simplex viru...

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Main Authors: Maija K. Pietilä, Jana J. Bachmann, Janne Ravantti, Lucas Pelkmans, Cornel Fraefel
Format: Article
Language:English
Published: Nature Portfolio 2023-07-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-40148-6
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author Maija K. Pietilä
Jana J. Bachmann
Janne Ravantti
Lucas Pelkmans
Cornel Fraefel
author_facet Maija K. Pietilä
Jana J. Bachmann
Janne Ravantti
Lucas Pelkmans
Cornel Fraefel
author_sort Maija K. Pietilä
collection DOAJ
description Abstract Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of this heterogeneity has yet to be clarified. To study the multimodal response of single human cells to herpes simplex virus type 1 (HSV-1) infection, we mapped high-dimensional viral and cellular state spaces throughout the infection using multiplexed imaging and quantitative single-cell measurements of viral and cellular mRNAs and proteins. Here we show that the high-dimensional cellular state scape can predict heterogenous infections, and cells move through the cellular state landscape according to infection progression. Spatial information reveals that infection changes the cellular state of both infected cells and of their neighbors. The multiplexed imaging of HSV-1-induced cellular modifications links infection progression to changes in signaling responses, transcriptional activity, and processing bodies. Our data show that multiplexed quantification of responses at the single-cell level, across thousands of cells helps predict infections and identify new targets for antivirals.
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spelling doaj.art-52f9a97fca50424ab7fd6e2d51df79752023-07-30T11:20:19ZengNature PortfolioNature Communications2041-17232023-07-0114112010.1038/s41467-023-40148-6Cellular state landscape and herpes simplex virus type 1 infection progression are connectedMaija K. Pietilä0Jana J. Bachmann1Janne Ravantti2Lucas Pelkmans3Cornel Fraefel4Institute of Virology, University of ZurichInstitute of Virology, University of ZurichMolecular and Integrative Biosciences Research Programme, University of HelsinkiDepartment of Molecular Life Sciences, University of ZurichInstitute of Virology, University of ZurichAbstract Prediction, prevention and treatment of virus infections require understanding of cell-to-cell variability that leads to heterogenous disease outcomes, but the source of this heterogeneity has yet to be clarified. To study the multimodal response of single human cells to herpes simplex virus type 1 (HSV-1) infection, we mapped high-dimensional viral and cellular state spaces throughout the infection using multiplexed imaging and quantitative single-cell measurements of viral and cellular mRNAs and proteins. Here we show that the high-dimensional cellular state scape can predict heterogenous infections, and cells move through the cellular state landscape according to infection progression. Spatial information reveals that infection changes the cellular state of both infected cells and of their neighbors. The multiplexed imaging of HSV-1-induced cellular modifications links infection progression to changes in signaling responses, transcriptional activity, and processing bodies. Our data show that multiplexed quantification of responses at the single-cell level, across thousands of cells helps predict infections and identify new targets for antivirals.https://doi.org/10.1038/s41467-023-40148-6
spellingShingle Maija K. Pietilä
Jana J. Bachmann
Janne Ravantti
Lucas Pelkmans
Cornel Fraefel
Cellular state landscape and herpes simplex virus type 1 infection progression are connected
Nature Communications
title Cellular state landscape and herpes simplex virus type 1 infection progression are connected
title_full Cellular state landscape and herpes simplex virus type 1 infection progression are connected
title_fullStr Cellular state landscape and herpes simplex virus type 1 infection progression are connected
title_full_unstemmed Cellular state landscape and herpes simplex virus type 1 infection progression are connected
title_short Cellular state landscape and herpes simplex virus type 1 infection progression are connected
title_sort cellular state landscape and herpes simplex virus type 1 infection progression are connected
url https://doi.org/10.1038/s41467-023-40148-6
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