1. Computational and Systems Biology
  2. Microbiology and Infectious Disease
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HSV-1 single cell analysis reveals anti-viral and developmental programs activation in distinct sub-populations

  1. Nir Drayman  Is a corresponding author
  2. Parthiv Patel
  3. Luke Vistain
  4. Savas Tay  Is a corresponding author
  1. University of Chicago, United States
Research Article
  • Cited 23
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Cite this article as: eLife 2019;8:e46339 doi: 10.7554/eLife.46339

Abstract

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 involves the recruitment of b-catenin to 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.

Article and author information

Author details

  1. Nir Drayman

    Institute of Molecular Engineering, University of Chicago, Chicago, United States
    For correspondence
    nirdra@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4460-9558
  2. Parthiv Patel

    Institute of Molecular Engineering, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Luke Vistain

    Institute of Molecular Engineering, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Savas Tay

    Institute of Molecular Engineering, University of Chicago, Chicago, United States
    For correspondence
    tays@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.

Funding

Human Frontier Science Program (post-doctoral fellowship)

  • Nir Drayman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Karla Kirkegaard, Stanford University School of Medicine, United States

Publication history

  1. Received: February 22, 2019
  2. Accepted: May 11, 2019
  3. Accepted Manuscript published: May 15, 2019 (version 1)
  4. Version of Record published: June 14, 2019 (version 2)

Copyright

© 2019, Drayman et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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