Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases

Daniela Michlmayr, Theodore R. Pak, Adeeb H. Rahman, El Ad David Amir, Eun Young Kim, Seunghee Kim-Schulze, Maria Suprun, Michael G. Stewart, Guajira P. Thomas, Angel Balmaseda, Li Wang, Jun Zhu, Mayte Suaréz-Fariñas, Steven M. Wolinsky, Andrew Kasarskis, Eva Harris*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes global epidemics of debilitating disease worldwide. To gain functional insight into the host cellular genes required for virus infection, we performed whole-blood RNA-seq, 37-plex mass cytometry of peripheral blood mononuclear cells (PBMCs), and serum cytokine measurements of acute- and convalescent-phase samples obtained from 42 children naturally infected with CHIKV. Semi-supervised classification and clustering of single-cell events into 57 sub-communities of canonical leukocyte phenotypes revealed a monocyte-driven response to acute infection, with the greatest expansions in “intermediate” CD14 ++ CD16 + monocytes and an activated subpopulation of CD14 + monocytes. Increases in acute-phase CHIKV envelope protein E2 expression were highest for monocytes and dendritic cells. Serum cytokine measurements confirmed significant acute-phase upregulation of monocyte chemoattractants. Distinct transcriptomic signatures were associated with infection timepoint, as well as convalescent-phase anti-CHIKV antibody titer, acute-phase viremia, and symptom severity. We present a multiscale network that summarizes all observed modulations across cellular and transcriptomic levels and their interactions with clinical outcomes, providing a uniquely global view of the biomolecular landscape of human CHIKV infection.

Original languageEnglish (US)
Article numbere7862
JournalMolecular Systems Biology
Volume14
Issue number8
DOIs
StatePublished - Aug 2018

Keywords

  • CyTOF
  • RNA-seq
  • chikungunya
  • immune profiling
  • pediatric

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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