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Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program

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Item Type:Article
Title:Single-cell RNA-sequencing of herpes simplex virus 1-infected cells connects NRF2 activation to an antiviral program
Creators Name:Wyler, E. and Franke, V. and Menegatti, J. and Kocks, C. and Boltengagen, A. and Praktiknjo, S. and Walch-Rückheim, B. and Bosse, J. and Rajewsky, N. and Grässer, F. and Akalin, A. and Landthaler, M.
Abstract:Herpesvirus infection initiates a range of perturbations in the host cell, which remain poorly understood at the level of individual cells. Here, we quantify the transcriptome of single human primary fibroblasts during the first hours of lytic infection with HSV-1. By applying a generalizable analysis scheme, we define a precise temporal order of early viral gene expression and propose a set-wise emergence of viral genes. We identify host cell genes and pathways relevant for infection by combining three different computational approaches: gene and pathway overdispersion analysis, prediction of cell-state transition probabilities, as well as future cell states. One transcriptional program, which correlates with increased resistance to infection, implicates the transcription factor NRF2. Consequently, Bardoxolone methyl and Sulforaphane, two known NRF2 agonists, impair virus production, suggesting that NRF2 activation restricts viral infection. Our study provides insights into early stages of HSV-1 infection and serves as a general blueprint for the investigation of heterogeneous cell states in virus infection.
Keywords:Fibroblasts, Gene Expression Profiling, Gene Regulatory Networks, Herpes Simplex, Host-Pathogen Interactions, Human Herpesvirus 1, Isothiocyanates, NF-E2-Related Factor 2, Oleanolic Acid, Primary Cell Culture, RNA Sequence Analysis, Single-Cell Analysis, Virus Replication
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:4878
Date:25 October 2019
Official Publication:https://doi.org/10.1038/s41467-019-12894-z
PubMed:View item in PubMed
Related to:
https://edoc.mdc-berlin.de/18123/Preprint version

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