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.

• Authors: Daniela Michlmayr, Eun-Young Kim, Adeeb H Rahman, Rohit Raghunathan, Seunghee Kim-Schulze, Yan Che, Selim Kalayci, Zeynep H Gümüş, Guillermina Kuan, Angel Balmaseda, Andrew Kasarskis, Steven M Wolinsky, Mayte Suaréz-Fariñas, Eva Harris
• Journal: Cell reports (Cell Rep) Vol. 31 Issue 4 Pg. 107569 (04 28 2020) ISSN: 2211-1247 [Electronic] United States
• PMID: 32348760 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Topics

• Acute Disease
• Child
• Dengue Virus (pathogenicity)
• Female
• Humans
• Immunity, Innate (immunology)
• Male
• Monocytes (virology)
• Zika Virus (pathogenicity)