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Title: Zika virus infection preferentially counterbalances human peripheral monocyte and/or NK cell activity
Authors: Lum, Fok-Moon
Lee, David
Chua, Tze-Kwang
Tan, Jeslin J.L.
Lee, Cheryl Y. P.
Liu, Xuan
Fang, Yongxiang
Lee, Bernett
Yee, Wearn-Xin
Rickett, Natasha Y.
Chia, Po-Ying
Lim, Vanessa
Leo, Yee-Sin
Matthews, David A.
Hiscox, Julian A.
Ng, Lisa F. P.
Keywords: Science::Medicine
Issue Date: 2018
Source: Lum, F.-M., Lee, D., Chua, T.-K., Tan, J. J. L., Lee, C. Y. P., Liu, X., … Ng, L. F. P. (2018). Zika virus infection preferentially counterbalances human peripheral monocyte and/or NK cell activity. mSphere, 3(2), e00120-18-. doi:10.1128/mspheredirect.00120-18
Journal: mSphere
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. 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.
ISSN: 2379-5042
DOI: 10.1128/mSphereDirect.00120-18
Rights: © 2018 Lum et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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