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

• Main Authors: Lum, Fok-Moon, Lee, Bernett, Lye, David Chien Boon, Tan, Jeslin J. L., Siti N. Amrun, Chia, Po-Ying, Chua, Tze-Kwang, Kam, Yiu-Wing, Yee, Wearn-Xin, Ling, Wei-Ping, Mok, Esther W. H., Chong, Chia-Yin, Leo, Yee-Sin, Ng, Lisa F. P., Lim, Vanessa W. X., Pang, Vincent J. X.
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2019
• Subjects: Zika Virus; Patient Cohort; Science::Medicine
• Online Access: https://hdl.handle.net/10356/87188; http://hdl.handle.net/10220/49882
• Institution: Nanyang Technological University

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 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. 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.