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. IMPORTANCE ZIKV reemerged in recent years, causing outbreaks in many parts of the world. Alarmingly,
ZIKV infection has been associated with neurological complications such as
Guillain-Barré syndrome (GBS) in adults and congenital fetal growth-associated anomalies in newborns. Host peripheral immune cells are one of the first to interact with the virus upon successful transmission from an infected female Aedes mosquito. However, little is known about the role of these immune cells during
infection. In this work, the immune responses of monocytes, known target cells of
ZIKV infection, were investigated by high-density transcriptomics. The analysis saw a robust immune response being elicited. Importantly, it also divulged that monocytes prime NK cell activities during
virus infection. Removal of monocytes during the
infection changed the immune milieu, which in turn reduced NK cell stimulation. This study provides valuable insights into the pathobiology of the virus and allows for the possibility of designing novel targeted
therapeutics.