Abstract
Zika virus (ZIKV) has re-emerged in the population and caused unprecedented global outbreaks. Here, the transcriptomic consequences of ZIKV infection were studied systematically firstly 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 crosstalk between monocytes and natural killer (NK) cells as one of the highly identified pathway. Immune-phenotyping 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 IFNγ 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 Zika virus (ZIKV), an infectious agent, which has re-emerged over the recent years, has been associated with causing congenital brain deformities. While numerous studies have focused on understanding the mechanisms of ZIKV pathogenesis, little knowledge is available for describing host cell immune response during active infection. ZIKV is transmitted via the bites of infected female Aedes mosquitoes and subsequently travels to the blood stream where it will encounter the peripheral immune cells. Recent studies have shown that the blood monocytes are targets of ZIKV, and thus understanding the response of these cells during infection would be critical as virus-host interaction determines disease progression. The significance of this study highlights the important immune pathways elicited by the monocytes during infection and further provides a model for the functional study of these cells and their fellow immune partners, with implications for the development of future immune-based therapies.