Single-cell transcriptional dynamics of flavivirus infection
Abstract
Dengue and Zika viral infections affect millions of people annually and can be complicated by hemorrhage 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.
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Author details
Funding
National Institute of Allergy and Infectious Diseases (1U19 AI10966201)
- Shirit Einav
Stanford Bio-X
- Shirit Einav
Stanford Institute for Immunity, Transplantation, and Infection
- Shirit Einav
European Molecular Biology Organization (ALTF 269-2016)
- Fabio Zanini
Child Health Research Institute
- Szu-Yuan Pu
Lucile Packard Foundation for Children's Health
- Szu-Yuan Pu
Stanford Clinical and Translational Science Award (UL1 TR000093)
- Szu-Yuan Pu
National Institute of Allergy and Infectious Diseases (5T32AI007502)
- Elena Bekerman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Zanini 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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