Virus Expression Database

GSE126042

Single cell analysis of HSV-1 infection reveals anti-viral and developmental programs are activated in distinct sub-populations with opposite outcomes

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.

13 Samples

ID Title Cell Type Timepoint Reported Virus Virus Species Exclusion Reason
GSM3589642 mock - dropseq Wrong technology
single cell RNA seq
GSM3589643 wt - dropseq Wrong technology
single cell RNA seq
GSM3589644 d0 - dropseq Wrong technology
single cell RNA seq
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