@article{80ff06037081423590db24ddeb8b06f5,
title = "Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection",
abstract = "Zika virus (ZIKV) is an emerging, mosquito-borne flavivirus responsible for recent epidemics across the Americas, and it is closely related to dengue virus (DENV). Here, we study samples from 46 DENV-naive and 43 DENV-immune patients with RT-PCR-confirmed ZIKV infection at early-acute, late-acute, and convalescent time points from our pediatric cohort study in Nicaragua. We analyze the samples via RNA sequencing (RNA-seq), CyTOF, and multiplex cytokine/chemokine Luminex to generate a comprehensive, innate immune profile during ZIKV infection. Immunophenotyping and analysis of cytokines/chemokines reveal that CD14+ monocytes play a key role during ZIKV infection. Further, we identify CD169 (Siglec-1) on CD14+ monocytes as a potential biomarker of acute ZIKV infection. Strikingly distinct transcriptomic and immunophenotypic signatures are observed at all three time points. Interestingly, pre-existing dengue immunity has minimal impact on the innate immune response to Zika. Finally, this comprehensive immune profiling and network analysis of ZIKV infection in children serves as a valuable resource. At three time points after Zika virus infection, Michlmayr et al. perform comprehensive immunoprofiling of pediatric cohort samples via RNA-seq, CyTOF, and Luminex cytokine/chemokine array, resulting in distinct temporal patterns of gene expression, cell profiles, and cytokines/chemokines. They show CD14+ monocytes play a central role, identify CD169 as a potential biomarker of acute ZIKV infection along with upregulation of CXCL10, and find no impact of prior dengue virus infection on the innate immune response to Zika.",
keywords = "CyTOF, Luminex, RNA-seq, Zika virus, biomarker, dengue virus, immune profiling, innate immunity, monocytes, network model",
author = "Daniela Michlmayr and Kim, {Eun Young} and Rahman, {Adeeb H.} and Rohit Raghunathan and Seunghee Kim-Schulze and Yan Che and Selim Kalayci and G{\"u}m{\"u}{\c s}, {Zeynep H.} and Guillermina Kuan and Angel Balmaseda and Andrew Kasarskis and Wolinsky, {Steven M.} and Mayte Suar{\'e}z-Fari{\~n}as and Eva Harris",
note = "Funding Information: This work was supported by grants U19AI118610 (E.H.) and P01AI106695 (E.H.) from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). We thank Michael Stewart for help with RNA isolation and sequencing and Theodore Pak and Li Wang for their constructive comments on the manuscript and data analysis. We also thank study personnel at the Centro de Salud S{\'o}crates Flores Vivas, the National Virology Laboratory of the Nicaraguan Ministry of Health, and the Sustainable Sciences Institute in Managua, Nicaragua. Finally, we are grateful to the study participants and their families. D.M. and E.H. designed the study and selected study participants. E.H. and A.B. directed studies in Nicaragua to obtain samples for this study. A.H.R. and D.M. performed CyTOF experiments, S.K.-S. and D.M. performed Luminex experiments, and A.H.R. performed CyTOF data analysis. E.-Y.K. and Y.C. performed RNA-seq experiments, and E.-Y.K. M.S.-F. and S.M.W. analyzed RNA-Seq data. M.S.-F. and A.K. designed the systems biology analytic approach, and R.R. S.K. Z.H.G. and M.S.-F. performed the statistical and bioinformatics analysis. D.M. and M.S.-F. wrote the first draft of the manuscript and prepared the figures, and D.M. M.S.-F. A.K. and E.H. revised the manuscript. All authors reviewed and approved the final version of the manuscript. The authors declare no competing interests. Funding Information: This work was supported by grants U19AI118610 (E.H.) and P01AI106695 (E.H.) from the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH). We thank Michael Stewart for help with RNA isolation and sequencing and Theodore Pak and Li Wang for their constructive comments on the manuscript and data analysis. We also thank study personnel at the Centro de Salud S{\'o}crates Flores Vivas, the National Virology Laboratory of the Nicaraguan Ministry of Health, and the Sustainable Sciences Institute in Managua, Nicaragua. Finally, we are grateful to the study participants and their families. Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = apr,
day = "28",
doi = "10.1016/j.celrep.2020.107569",
language = "English (US)",
volume = "31",
journal = "Cell reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}
