Longitudinal Study Of Cellular And Systemic Cytokine Signatures To Define The Dynamics Of A Balanced Immune Environment During Disease Manifestation In Zika Virus-Infected Patients

Background. Since its unexpected reemergence, Zika virus (ZIKV) has caused numerous outbreaks globally. This study characterized the host immune responses during ZIKV infection.Methods. 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.Results. 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 gamma-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 gamma-induced protein 10, interferon gamma, 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.Conclusions. 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.