Abstract
Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection. Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Plasma immune mediators were profiled via multiplex microbead assay, while changes in blood cell numbers were determined with immunophenotyping. Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes. Importantly, viremic patients experiencing moderate symptoms had significantly higher quantities of interferon γ-induced protein 10, monocyte chemotactic protein 1, interleukin 1 receptor antagonist, interleukin 8, and placental growth factor 1, accompanied by reduced numbers of peripheral CD8+ T cells, CD4+ T cells, and double-negative T cells. Levels of T-cell associated mediators, including interferon γ-induced protein 10, interferon γ, and interleukin 10, were high in recovery phases of ZIKV infection, suggesting a functional role for T cells. The identification of different markers at specific disease phases emphasizes the dynamics of a balanced cytokine environment in disease progression. This is the first comprehensive study that highlights specific cellular changes and immune signatures during ZIKV disease progression, and it provides valuable insights into ZIKV immunopathogenesis.
Highlights
Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally
Data showed the involvement of various immune mediators during acute ZIKV infection accompanied by a general reduction in blood cell numbers for all immune subsets except CD14+ monocytes
ZIKV is an arbovirus transmitted via the bite of infected Aedes mosquitoes, non–vector‐borne transmissions such as sexual, maternal-fetal, and blood transfusion transmissions have been reported [4,5,6,7]
Summary
Patient samples were collected longitudinally during the acute, convalescence and recovery phases of ZIKV infection over 6 months during the Singapore outbreak in late 2016. Collection of blood samples from healthy donors was done with written consent in accordance with guidelines from the Health Sciences Authority of Singapore (study approval number National University Singapore Institutional Review Board approval 10-250). The first case of ZIKV infection was reported on 27 August 2016 [15], and detection was confirmed by ZIKV-specific quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis [16]. ZIKV infection was confirmed by a positive result of ZIKV-specific RT-PCR analysis of whole-blood specimens. Samples from healthy donors were included and prescreened for the presence of ZIKV viral RNA [16] and ZIKV-specific antibodies [17]. All healthy donors were nonfebrile and had no signs of acute illness during recruitment
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