Extreme heterogeneity of influenza virus infection in single cells
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.
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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.
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.
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