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Abstract
Zika virus (ZIKV) has reemerged in the population and caused unprecedented global outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied systematically first in human peripheral blood CD14+ monocytes and monocyte-derived macrophages with high-density RNA sequencing. Analyses of the ZIKV genome revealed that the virus underwent genetic diversification, and differential mRNA abundance was found in host cells during infection. Notably, there was a significant change in the cellular response, with cross talk between monocytes and natural killer (NK) cells as one of the highly identified pathways. Immunophenotyping of peripheral blood from ZIKV-infected patients further confirmed the activation of NK cells during acute infection. ZIKV infection in peripheral blood cells isolated from healthy donors led to the induction of gamma interferon (IFN-γ) and CD107a- two key markers of NK cell function. Depletion of CD14+ monocytes from peripheral blood resulted in a reduction of these markers and reduced priming of NK cells during infection. This was complemented by the immunoproteomic changes observed. Mechanistically, ZIKV infection preferentially counterbalances monocyte and/or NK cell activity, with implications for targeted cytokine immunotherapies.
Original language | English |
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Article number | e00120-18 |
Journal | mSphere |
Volume | 3 |
Issue number | 2 |
DOIs | |
Publication status | Published - 28 Mar 2018 |
Keywords
- Immune response
- Monocytes
- NK cells
- RNA-seq
- Transcriptomes
- Zika virus
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Adapting high throughput technologies to understand the process of viral zoonosis
Matthews, D. A. (Principal Investigator)
4/01/16 → 3/01/20
Project: Research