Submitted by Nir Drayman (University of Chicago, USA) on Feb 04 2019
Platform: ngs – Illumina HiSeq 4000 (Homo sapiens)
Pubmed: 31090537
Summary Viral infection is usually studied at the population level by averaging over millions of cells. However, infection at the single-cell level is highly heterogeneous, where most infected cells give rise to none or few viral progeny while some cells produce thousands. Analysis of HSV-1 infection by population averaged measurements has taught us a lot about the course of viral infection, but has also produced contradictory results, such as the concurrent activation and inhibition of type I interferon signaling during infection. Here, we combine live-cell imaging and single-cell RNA sequencing to characterize viral and host transcriptional heterogeneity during HSV-1 infection of primary human cells. We find extreme variability in the level of viral gene expression among individually infected cells and show that they cluster into transcriptionally distinct sub-populations. We find that anti-viral signaling is initiated in a rare group of abortively infected cells, while highly infected cells undergo cellular reprogramming to an embryonic-like transcriptional state. This reprogramming includes the re-localization of b-catenin into the host nucleus and viral replication compartments and is required for late viral gene expression and progeny production. These findings uncover the transcriptional differences in cells with variable infection outcomes and shed new light on the manipulation of host pathways by HSV-1.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
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GSM3589642 | mock - dropseq | Wrong technology single cell RNA seq |
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GSM3589643 | wt - dropseq | Wrong technology single cell RNA seq |
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GSM3589644 | d0 - dropseq | Wrong technology single cell RNA seq |
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GSM3589645 | mock - sorted rep1 | dermal fibroblast | mock | Uninfected | ||
GSM3589646 | mock - sorted rep2 | dermal fibroblast | mock | Uninfected | ||
GSM3589647 | wt - sorted icp4 negative rep1 | dermal fibroblast | unknown | HSV-1 | Human alphaherpesvirus 1 | |
GSM3589648 | wt - sorted icp4 negative rep2 | dermal fibroblast | unknown | HSV-1 | Human alphaherpesvirus 1 | |
GSM3589649 | wt - sorted icp4 positive rep1 | dermal fibroblast | unknown | HSV-1 | Human alphaherpesvirus 1 | |
GSM3589650 | wt - sorted icp4 positive rep2 | dermal fibroblast | unknown | HSV-1 | Human alphaherpesvirus 1 | |
GSM3589651 | d0 - sorted icp4 negative rep1 | dermal fibroblast | unknown | HSV-1 | Human alphaherpesvirus 1 | Extra interventions mutant HSV - dICP0 |
GSM3589652 | d0 - sorted icp4 negative rep2 | dermal fibroblast | unknown | HSV-1 | Human alphaherpesvirus 1 | Extra interventions mutant HSV - dICP0 |
GSM3589653 | d0 - sorted icp4 positive rep1 | dermal fibroblast | unknown | HSV-1 | Human alphaherpesvirus 1 | Extra interventions mutant HSV - dICP0 |
GSM3589654 | d0 - sorted icp4 positive rep2 | dermal fibroblast | unknown | HSV-1 | Human alphaherpesvirus 1 | Extra interventions mutant HSV - dICP0 |