1. Microbiology and Infectious Disease
Download icon

Extreme heterogeneity of influenza virus infection in single cells

  1. Alistair B Russell
  2. Cole Trapnell
  3. Jesse D Bloom  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
  2. University of Washington, United States
Research Article
  • Cited 5
  • Views 3,546
  • Annotations
Cite as: eLife 2018;7:e32303 doi: 10.7554/eLife.32303

Abstract

Viral infection can dramatically alter a cell's transcriptome. However, these changes have mostly been studied by bulk measurements on many cells. Here we use single-cell mRNA sequencing to examine the transcriptional consequences of influenza virus infection. We find extremely wide cell-to-cell variation in the productivity of viral transcription - viral transcripts comprise less than a percent of total mRNA in many infected cells, but a few cells derive over half their mRNA from virus. Some infected cells fail to express at least one viral gene, but this gene absence only partially explains variation in viral transcriptional load. Despite variation in viral load, the relative abundances of viral mRNAs are fairly consistent across infected cells. Activation of innate immune pathways is rare, but some cellular genes co-vary in abundance with the amount of viral mRNA. Overall, our results highlight the complexity of viral infection at the level of single cells.

Article and author information

Author details

  1. Alistair B Russell

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0002-5342-2309

  2. Cole Trapnell

    Department of Genome Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Jesse D Bloom

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    jbloom@fredhutch.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0003-1267-3408

Funding

National Institute of General Medical Sciences (R01GM102198)

  • Jesse D Bloom

National Institute of Allergy and Infectious Diseases (AI127897)

  • Jesse D Bloom

Damon Runyon Cancer Research Foundation (Postdoctoral Fellowship)

  • Alistair B Russell

Burroughs Wellcome Fund (Young Investigator in the Pathogenesis of Infectious Diseases)

  • Jesse D Bloom

Simons Foundation (Faculty Scholar Award)

  • Jesse D Bloom

Howard Hughes Medical Institute (Faculty Scholar Award)

  • Jesse D Bloom

Eunice Kennedy Shriver National Institute of Child Health and Human Development (DP2OD020868)

  • Cole Trapnell

William Keck Foundation (Keck Foundation Grant)

  • Cole Trapnell

Alfred P. Sloan Foundation (Sloan Research Fellowship)

  • Cole Trapnell

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

Reviewing Editor

  1. Arup K Chakraborty, Reviewing Editor, Massachusetts Institute of Technology, United States

Publication history

  1. Received: September 26, 2017
  2. Accepted: January 31, 2018
  3. Accepted Manuscript published: February 16, 2018 (version 1)
  4. Version of Record published: February 26, 2018 (version 2)

Copyright

© 2018, Russell 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.

Metrics

  • 3,546
    Page views
  • 739
    Downloads
  • 5
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Research organisms

Further reading

    1. Microbiology and Infectious Disease

    Single-cell transcriptional dynamics of flavivirus infection

    Fabio Zanini et al.
    Research Article Updated

    Dengue and Zika viral infections affect millions of people annually and can be complicated by hemorrhage and shock or neurological manifestations, respectively. However, a thorough understanding of the host response to these viruses is lacking, partly because conventional approaches ignore heterogeneity in virus abundance across cells. We present viscRNA-Seq (virus-inclusive single cell RNA-Seq), an approach to probe the host transcriptome together with intracellular viral RNA at the single cell level. We applied viscRNA-Seq to monitor dengue and Zika virus infection in cultured cells and discovered extreme heterogeneity in virus abundance. We exploited this variation to identify host factors that show complex dynamics and a high degree of specificity for either virus, including proteins involved in the endoplasmic reticulum translocon, signal peptide processing, and membrane trafficking. We validated the viscRNA-Seq hits and discovered novel proviral and antiviral factors. viscRNA-Seq is a powerful approach to assess the genome-wide virus-host dynamics at single cell level.

    1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    Neolithic and medieval virus genomes reveal complex evolution of hepatitis B

    Ben Krause-Kyora et al.
    Short Report Updated
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Synergy in anti-malarial pre-erythrocytic and transmission-blocking antibodies is achieved by reducing parasite density

    Ellie Sherrard-Smith et al.
    Research Article