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

Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases.

Author information

1
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California Berkeley, Berkeley, CA, USA.
2
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
3
Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
4
Division of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
5
Department of Population Health and Science Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
6
Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministerio de Salud, Managua, Nicaragua.
7
Division of Infectious Diseases and Vaccinology, School of Public Health, University of California Berkeley, Berkeley, CA, USA eharris@berkeley.edu.

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.

KEYWORDS:

CyTOF; RNA‐seq; chikungunya; immune profiling; pediatric

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