Comprehensive innate immune profiling of chikungunya virus infection in pediatric cases

Molecular Systems Biology
Daniela MichlmayrEva Harris

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 level...Continue Reading

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Datasets Mentioned

BETA
GSE99992

Methods Mentioned

BETA
ELISA
flow cytometry
FCS
Assay
PCR
chip

Software Mentioned

StringTie
Beadview
clusterCrit R
coexpp
pheatmap
HISAT2
MetaHybridLouvain
Gephi
pathview
‐ Toolkit

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