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| Status |
Public on Mar 20, 2024 |
| Title |
Single-cell analysis reveals an antiviral network that controls Zika virus infection in human dendritic cells |
| Organisms |
Chlorocebus aethiops; Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Zika virus (ZIKV) is a mosquito-borne flavivirus that caused an epidemic in the Americas in 2016 and is linked to severe neonatal birth defects, including microcephaly and spontaneous abortion. To better understand the host response to ZIKV infection, we adapted the 10x Genomics Chromium single cell RNA sequencing (scRNA-seq) assay to simultaneously capture viral RNA and host mRNA. Using this assay, we profiled the antiviral landscape in a population of human moDCs infected with ZIKV at the single cell level. The bystander cells, which lacked detectable viral RNA, expressed an antiviral state that was enriched for genes coinciding predominantly with a type I interferon (IFN) response. Within the infected cells, viral RNA negatively correlated with type I IFN dependent and independent genes (antiviral module). We modeled the ZIKV specific antiviral state at the protein level leveraging experimentally derived protein-interaction data. We identified a highly interconnected network between the antiviral module and other host proteins. In this work, we propose a new paradigm for the antiviral response to a specific virus, combining an unbiased list of genes that highly correlate with viral RNA on a per cell basis with experimental protein interaction data. Our ZIKV-inclusive scRNA-seq assay will serve as a useful tool to gaining greater insight into the host response to ZIKV and can be applied more broadly to the flavivirus field.
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| Overall design |
Experiment 1 consisted of 4 pools of 1:1 mixed mock infected and ZIKV infected VeroE6 cells with varying (0, 0.1, 1, 10 µM) concentrations of ZIKV-specific primer
Experiment 2 consisted of 4 pools of 1:2 mixed mock infected and (mock infected/IFN-β treated/primer; ZIKV infected/no treatment/primer; ZIKV infected/IFN-β treated/primer; ZIKV infected/IFN-β treated/no primer )
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| Web link |
https://doi.org/10.1128/jvi.00194-24
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| Contributor(s) |
Moore KM, Pelletier A, Lapp S, Metz A, Tharp GK, Lee M, Bhasin SS, Bhasin M, Sékaly R, Bosinger SE, Suthar MS |
| Citation(s) |
38567950 |
| |
| Submission date |
Apr 25, 2023 |
| Last update date |
Jun 19, 2024 |
| Contact name |
Gregory K Tharp |
| E-mail(s) |
gktharp@emory.edu
|
| Phone |
404-727-7797
|
| Organization name |
Yerkes National Primate Research Center
|
| Department |
Developmental and Cognitive Neuroscience
|
| Lab |
Genomics Core
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| Street address |
954 Gatewood Dr
|
| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30329-4208 |
| Country |
USA |
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| Platforms (2) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
| GPL29682 |
Illumina NovaSeq 6000 (Chlorocebus aethiops) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA961779 |
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