Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection

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*

*Corresponding author for this work

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number107569
JournalCell reports
Volume31
Issue number4
DOIs
StatePublished - Apr 28 2020

Keywords

  • biomarker
  • CyTOF
  • dengue virus
  • immune profiling
  • innate immunity
  • Luminex
  • monocytes
  • network model
  • RNA-seq
  • Zika virus

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Fingerprint Dive into the research topics of 'Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection'. Together they form a unique fingerprint.

  • Cite this

    Michlmayr, D., Kim, E. Y., Rahman, A. H., Raghunathan, R., Kim-Schulze, S., Che, Y., Kalayci, S., Gümüş, Z. H., Kuan, G., Balmaseda, A., Kasarskis, A., Wolinsky, S. M., Suaréz-Fariñas, M., & Harris, E. (2020). Comprehensive Immunoprofiling of Pediatric Zika Reveals Key Role for Monocytes in the Acute Phase and No Effect of Prior Dengue Virus Infection. Cell reports, 31(4), [107569]. https://doi.org/10.1016/j.celrep.2020.107569