Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases

Mol Syst Biol. 2018 Aug 27;14(8):e7862. doi: 10.15252/msb.20177862.


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.

Keywords: CyTOF; RNA‐seq; chikungunya; immune profiling; pediatric.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Animals
  • Cell Lineage / genetics
  • Cell Lineage / immunology
  • Chikungunya Fever / genetics*
  • Chikungunya Fever / transmission
  • Chikungunya Fever / virology
  • Chikungunya virus / genetics*
  • Chikungunya virus / immunology
  • Chikungunya virus / pathogenicity
  • Child
  • Child, Preschool
  • Culicidae / virology
  • Cytokines / blood
  • Cytokines / genetics
  • Dendritic Cells / immunology
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Humans
  • Immunity, Innate / genetics*
  • Infant
  • Infant, Newborn
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Monocytes / immunology
  • Pediatrics
  • Receptors, IgG / genetics
  • Receptors, IgG / immunology
  • Sequence Analysis, RNA
  • Transcriptome / genetics*
  • Transcriptome / immunology


  • Cytokines
  • Lipopolysaccharide Receptors
  • Receptors, IgG