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